Updated on 2026/02/28

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写真a

 
Tomomi Sato
 
Organization
Graduate School of Nanobioscience Department of Life and Environmental System Science Professor
School of Science Department of Science
School of Science Dean
Title
Professor
Homepage
http://endocrin.sci.yokohama-cu.ac.jp/
Profile
出生前後のマウス生殖器官は発生、発達途中であり、この時期に性ホルモンを投与するとさまざまな生殖異常が生じる。これまでに、エストロゲン受容体ベータ型を介した卵巣特異的な作用を見いだし、その作用経路を解析している。
External link

Degree

  • Studies on cell proliferation and cell death in the female reproductive tracts of control and neonatally diethylstilbestrol-exposed mice. ( Yokohama City University )

Research Interests

  • 内分泌学

  • 生殖生物学

Research Areas

  • Life Science / Morphology and anatomical structure

Education

  • Yokohama City University   Graduate

    - 1997

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    Country： Japan

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  • Yokohama City University

    - 1991

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Research History

  • Yokohama City University International College of Arts and Sciences Life and Environmental Science Graduate School of Nanobioscience Department of Life and Environmental System Science   Professor

    2013

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  • Yokohama City University   International College of Arts and Sciences   Associate Professor

    2006 - 2013

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  • イリノイ大学   獣医生物科学教室   博士研究員

    1999 - 2001

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  • University of Illinois, Postdoctoral Research Associate

    1999 - 2001

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  • Yokohama City University   Research Associate

    1997 - 2006

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  • 日本学術振興会   特別研究員 (DC2)

    1996 - 1997

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  • 株式会社資生堂

    1993 - 1994

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Professional Memberships

  • JAPAN SOCIETY FOR COMPARATIVE ENDOCRINOLOGY

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  • Japan Society of Reproductive Endocrinology

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  • THE ZOOLOGICAL SOCIETY OF JAPAN

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  • The Society for the Study of Reproduction

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  • THE JAPAN SOCIETY FOR PITUITARY RESEARCH

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  • The Endocrine Society

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Committee Memberships

  • 内閣府食品安全委員会   器具・容器包装専門調査会 専門委員  

    2021.10   

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Papers

  • Deficiency of Estrogen Receptor 2 Expression Enhances Disorganization of the Mouse Uterus With Age. International journal

    Tadaaki Nakajima, Reina Arakawa, Saki Nose, Norika Matsuda, Airi Tsuge, Mami Ishii, Tomohiro Ishikawa, Yurika Tsurugai, Shinichi Miyagawa, Taisen Iguchi, Tomomi Sato

    Endocrinology   166 ( 8 )   2025.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    Constitutive stimulation of estrogen signaling in mice causes dilated uterine glands with activation of epithelial cell proliferation. In estrogen receptor β knockout (Esr2 KO) mice, cell proliferation in the uterine epithelium is permanently stimulated; therefore, we histologically analyzed the uterine structure in Esr2 KO mice with age. In the uterus of Esr2 KO mice, dilation of the uterine glands was accelerated and the collagen was accumulated in the stroma. The uterine glands were dilated with age even in wild-type (WT) mice; however, Esr2 KO accelerated the dilation of uterine glands quantitatively. The expression of FOXA2 transcription factor, which is essential for uterine glandular function, was diminished in dilated uterine glands of WT and Esr2 KO mice and decreased in the uterine glands of normal size in 12-month-old Esr2 KO mice. To investigate mechanisms of the collagen accumulation in the Esr2 KO uterus, we focused on collagen synthesis and degradation. In the uterine stroma of Esr2 KO mice, MMP8 expression in whole uteri and the number of MMP8-expressing macrophages were decreased. An analysis of the comprehensive gene expression suggested that increased expression of fibroblast growth factors and decreased expression of an aquaporin may be related to the dilation of uterine glands in Esr2 KO mice, and reduced infiltration or differentiation into the macrophages with MMP8 expression may be involved with the collagen accumulation in Esr2 KO mice with age. Taken together, the absence of ESR2 constitutively disrupts estrogen signaling and promotes aging in the uterus via stimulation of epithelial cell proliferation and a decrease of MMP8-expressing macrophages.

    DOI： 10.1210/endocr/bqaf103

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  • In silico screening system based on a transcription factors regulatory network only using transcriptomic data. International journal

    Tadaaki Nakajima, Kentaro Harada, Yasuhiro Tomooka, Tomomi Sato

    PloS one   20 ( 4 )   e0319971   2025

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    Language：English   Publishing type：Research paper (scientific journal)  

    In this study, we developed a method to identify core transcription factors (TFs) involved in differentiation using only comprehensive gene analysis. The theory of in silico screening using TFs regulatory network analysis (ISNA) required the following requirements: (1) estimating promoter regions, (2) constructing TFs regulatory network (TRN) relationships using the nucleotide sequence information in the promoters and score matrices derived from TF consensus sequences, and (3) identifying candidate core TFs by determining dissociation constants (Kd values) within the relationships of TRN. ISNA demonstrated the ability to predict the core TFs involved in the endothelial-to-mesenchymal transition of human umbilical vein endothelial cell (HUVEC) and the differentiation of human embryonic stem cells into mesodermal cells. Using ISNA, we identified HMGA2 as a novel core TF in uterine epithelium. Notably, HMGA2 expression was predominantly detected in uterine epithelium, where it regulated cell proliferation in response to estrogen. These findings highlight ISNA's potential to identify core TFs based on transcriptomic data.

    DOI： 10.1371/journal.pone.0319971

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  • Photodynamic Effect of Amphiphilic N∧C∧N-Coordinated Platinum(II) Complexes in Human Umbilical Vein Endothelial Cells. International journal

    Shingo Hattori, Mizuki Ogishima, Tadaaki Nakajima, Shota Hosoya, Yuichi Kitagawa, Yasuchika Hasegawa, Shinji Nonose, Tomomi Sato, Kazuteru Shinozaki

    Inorganic chemistry   63 ( 30 )   13972 - 13979   2024.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    Here, we report a photodynamic therapy (PDT) photosensitizer of N∧C∧N-coordinated Pt(II) complexes: [Pt(L)(solv)]+ (HL = 1,3-(2-dipyridyl)benzene) and [Pt(L)]+@HSA, which is the Pt(II) complex encapsulated in human serum albumin (HSA). The quantum yield of singlet oxygen production for [Pt(L)(solv)]+ is more than 50%, while that for [Pt(L)]+@HSA is much lower. Photoimages of human umbilical vein endothelial cells (HUVECs) treated with the Pt(II) complexes suggest that [Pt(L)(solv)]+ is delocalized in the entire cell after the fast uptake by diffusion and [Pt(L)]+@HSA is taken up by endocytosis and localized on organelles and the cell membrane. [Pt(L)(solv)]+ shows high photocytotoxicity for HUVECs, while [Pt(L)]+@HSA does not show photocytotoxicity.

    DOI： 10.1021/acs.inorgchem.4c01414

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  • Comparative analysis of gonadal transcriptomes between turtle and alligator identifies common molecular cues activated during the temperature-sensitive period for sex determination Reviewed

    Kenji Toyota, Hiroshi Akashi, Momoka Ishikawa, Katsushi Yamaguchi, Shuji Shigenobu, Tomomi Sato, Anke Lange, Charles R. Tyler, Taisen Iguchi, Shinichi Miyagawa

    Gene   888   147763 - 147763   2023.12

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.gene.2023.147763

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  • SMAD2/3 signaling regulates initiation of mouse Wolffian ducts and proximal differentiation in Müllerian ducts Reviewed International journal

    Tadaaki Nakajima, Akihiro Imai, Chihiro Ishii, Kota Tsuruyama, Risa Yamanaka, Yasuhiro Tomooka, Shinta Saito, Noritaka Adachi, Satomi Kohno, Tomomi Sato

    FEBS Open Bio   14 ( 1 )   37 - 50   2023.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.

    DOI： 10.1002/2211-5463.13729

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  • Evolutionary differentiation of androgen receptor ohnologs is responsible for the development of androgen-dependent unique sexual characteristics in a teleost fish Reviewed

    Yukiko Ogino, Satoshi Ansai, Eiji Watanabe, Masaki Yasugi, Yukitoshi Katayama, Hirotaka Sakamoto, Keigo Okamoto, Kataaki Okubo, Yasuhiro Yamamoto, Ikuyo HARA, Touko Yamazaki, Ai Kato, Yasuhiro Kamei, Kiyoshi Naruse, Kohei Ohta, Hajime Ogino, Tatsuya Sakamoto, Shinichi Miyagawa, TOMOMI SATO, Gen Yamada, Michael Baker, Taisen Iguchi

    Nature Communications   2023.3

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    Publisher：Research Square Platform LLC  

    Abstract

    Teleost fishes exhibit complex unique sexual characteristics, such as fin enlargement and courtship display, in response to androgens. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analysed medaka (Oryzias latipes) mutants deficient in androgen receptor ohnologs (ara and arb) generated by the teleost-specific whole-genome duplication event (TSGD). We discovered that both ar ohnologs are not required for spermatogenesis and appear to be functionally redundant for courtship display in males, while both copies were necessary for their reproductive success; ara was required for tooth enlargement and behavioural attractiveness, while arb for male-specific fin morphogenesis and sexual motivation. We further showed that the differences in both the transcription of the two ars, cellular localisation of their encoded proteins and their downstream genetic programs could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in the teleost lineage in two different ways: First through the loss of their roles in spermatogenesis and second through the gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.

    DOI： 10.21203/rs.3.rs-1848626/v1

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    Other Link： https://www.researchsquare.com/article/rs-1848626/v1.html

  • Effect of thyroid hormone-disrupting chemicals on swim bladder inflation and thyroid hormone-related gene expression in Japanese medaka and zebrafish. Reviewed International journal

    Yoshifumi Horie, Miho Nomura, Konori Okamoto, Chiho Takahashi, Tomomi Sato, Shinichi Miyagawa, Hideo Okamura, Taisen Iguchi

    Journal of applied toxicology : JAT   42 ( 8 )   1385 - 1395   2022.8

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    We compared the influence of thyroid hormone-disrupting chemicals (heptafluorobutanoic acid, PFBA and tris[1,3-dichloro-2-propyl] phosphate, TDCPP) and thyroid hormone (3,3',5-triiodo-L-thyronine, T3) on swim bladder inflation and thyroid hormone-related gene expression in Japanese medaka and zebrafish. The swim bladder of most larvae had inflated at 4 h post hatching (hph) in Japanese medaka and at 48 hph in zebrafish in controls. In both fish species, the swim bladder inflation was inhibited in larvae exposed to PFBA (lowest observed effect concentration [LOEC] in medaka: 40 mg/L; in zebrafish: 80 mg/L), TDCPP (LOEC in medaka: 1 mg/L; in zebrafish: 0.5 mg/L), and T3 (no inhibition in Japanese medaka; LOEC in zebrafish: 7.5 μg/L). We also examined the influence of PFBA, TDCPP, and T3 on the expression of thyroid stimulating hormone subunit beta (tshβ) or thyroid hormone receptor alpha (trα) and beta (trβ). No changes were observed in the expression of genes after PFBA and TDCPP exposure; however, T3 exposure upregulated trα and trβ expression in both fish species. When the results were compared between Japanese medaka and zebrafish, swim bladder inflation in both species was found to be inhibited by exposure to thyroid hormone-disrupting chemicals. Our results show that inhibition of the swim bladder inflation at 4 hph in Japanese medaka and 48 hph in zebrafish is a potential indicator of thyroid hormone-disturbing activity of chemicals.

    DOI： 10.1002/jat.4302

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  • Summary of 17 chemicals evaluated by OECD TG229 using Japanese Medaka, Oryzias latipes in EXTEND 2016. Reviewed International journal

    Yukio Kawashima, Yuta Onishi, Norihisa Tatarazako, Hirotaka Yamamoto, Masaaki Koshio, Tomohiro Oka, Yoshifumi Horie, Haruna Watanabe, Takashi Nakamoto, Jun Yamamoto, Hidenori Ishikawa, Tomomi Sato, Kunihiko Yamazaki, Taisen Iguchi

    Journal of applied toxicology : JAT   42 ( 5 )   750 - 777   2022.5

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    In June 2016, the Ministry of the Environment of Japan announced a program "EXTEND2016" on the implementation of testing and assessment for endocrine active chemicals, consisting of a two-tiered strategy. The aim of the Tier 1 screening and the Tier 2 testing is to identify the impacts on the endocrine system and to characterize the adverse effects to aquatic animals by endocrine disrupting chemicals detected in the aquatic environment in Japan. For the consistent assessment of the effects on reproduction associated with estrogenic, anti-estrogenic, androgenic, and/or anti-androgenic activities of chemicals throughout Tier 1 screening to Tier 2 testing, a unified test species, Japanese medaka (Oryzias latipes), has been used. For Tier 1 screening, the in vivo Fish Short-Term Reproduction Assay (OECD test guideline No. 229) was conducted for 17 chemicals that were nominated based on the results of environmental monitoring, existing knowledge obtained from a literature survey, and positive results in reporter gene assays using the estrogen receptor of Japanese medaka. In the 17 assays using Japanese medaka, adverse effects on reproduction (i.e., reduction in fecundity and/or fertility) were suggested for 10 chemicals, and a significant increase of hepatic vitellogenin in males, indicating estrogenic (estrogen receptor agonistic) potency, was found for eight chemicals at the concentrations in which no overt toxicity was observed. Based on these results, and the frequency and the concentrations detected in the Japanese environment, estrone, 4-nonylphenol (branched isomers), 4-tert-octylphenol, triphenyl phosphate, and bisphenol A were considered as high priority candidate substances for the Tier 2 testing.

    DOI： 10.1002/jat.4255

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  • Juvenile hormone synthesis and signaling disruption triggering male offspring induction and population decline in cladocerans (water flea): Review and adverse outcome pathway development. Reviewed International journal

    Kenji Toyota, Haruna Watanabe, Masashi Hirano, Ryoko Abe, Hitoshi Miyakawa, You Song, Tomomi Sato, Shinichi Miyagawa, Knut Erik Tollefsen, Hiroshi Yamamoto, Norihisa Tatarazako, Taisen Iguchi

    Aquatic toxicology (Amsterdam, Netherlands)   243   106058 - 106058   2022.2

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    Juvenile hormone (JH) are a family of multifunctional hormones regulating larval development, molting, metamorphosis, reproduction, and phenotypic plasticity in arthropods. Based on its importance in arthropod life histories, many insect growth regulators (IGRs) mimicking JH have been designed to control harmful insects in agriculture and aquaculture. These JH analogs (JHAs) may also pose hazards to nontarget species by causing unexpected endocrine-disrupting (ED) effects such as molting and metamorphosis defects, larval lethality, and disruption of the sexual identity. This critical review summarizes the current knowledge of the JH-mediated effects in the freshwater cladoceran crustaceans such as Daphnia species on JHA-triggered endocrine disruptive outputs to establish a systematic understanding of JHA effects. Based on the current knowledge, adverse outcome pathways (AOPs) addressing the JHA-mediated ED effects in cladoceran leading to male offspring production and subsequent population decline were developed. The weight of evidence (WoE) of AOPs was assessed according to established guidelines. The review and AOP development aim to present the current scientific understanding of the JH pathway and provide a robust reference for the development of tiered testing strategies and new risk assessment approaches for JHAs in future ecotoxicological research and regulatory processes.

    DOI： 10.1016/j.aquatox.2021.106058

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  • Summary of reference chemicals evaluated by the fish short-term reproduction assay, OECD TG229, using Japanese Medaka, Oryzias latipes. Reviewed International journal

    Yuta Onishi, Norihisa Tatarazako, Masaaki Koshio, Tetsuro Okamura, Haruna Watanabe, Atsushi Sawai, Jun Yamamoto, Hidenori Ishikawa, Tomomi Sato, Yukio Kawashima, Kunihiko Yamazaki, Taisen Iguchi

    Journal of applied toxicology : JAT   41 ( 8 )   1200 - 1221   2021.8

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    Under the Organisation for Economic Co-operation and Development (OECD), the Ministry of the Environment of Japan (MOE) added Japanese medaka (Oryzias latipes) to the test guideline fish short-term reproduction assay (FSTRA) developed by the United States Environmental Protection Agency (US EPA) using fathead minnow (Pimephales promelas). The FSTRA was designed to detect endocrine disrupting effects of chemicals interacting with the hypothalamic-pituitary-gonadal axis (HPG axis) such as agonists or antagonists on the estrogen receptor (Esr) and/or the androgen receptor (AR) and steroidogenesis inhibitors. We conducted the FSTRA with Japanese medaka, in accordance with OECD test guideline number 229 (TG229), for 16 chemicals including four Esr agonists, two Esr antagonists, three AR agonists, two AR antagonists, two steroidogenesis inhibitors, two progesterone receptor agonists, and a negative substance, and evaluated the usability and the validity of the FSTRA (TG229) protocol. In addition, in vitro reporter gene assays (RGAs) using Esr1 and ARβ of Japanese medaka were performed for the 16 chemicals, to support the interpretation of the in vivo effects observed in the FSTRA. In the present study, all the test chemicals, except an antiandrogenic chemical and a weak Esr agonist, significantly reduced the reproductive status of the test fish, that is, fecundity or fertility, at concentrations where no overt toxicity was observed. Moreover, vitellogenin (VTG) induction in males and formation of secondary sex characteristics (SSC), papillary processes on the anal fin, in females was sensitive endpoints to Esr and AR agonistic effects, respectively, and might be indicators of the effect concentrations in long-term exposure. Overall, it is suggested that the in vivo FSTRA supported by in vitro RGA data can adequately detect effects on the test fish, O. latipes, and probably identify the mode of action (MOA) of the chemicals tested.

    DOI： 10.1002/jat.4104

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  • Sex Determination and Differentiation in Decapod and Cladoceran Crustaceans: An Overview of Endocrine Regulation. Reviewed International journal

    Kenji Toyota, Hitoshi Miyakawa, Chizue Hiruta, Tomomi Sato, Hidekazu Katayama, Tsuyoshi Ohira, Taisen Iguchi

    Genes   12 ( 2 )   2021.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are particularly diverse among the Arthropoda and contain a wide variety of commercially important fishery species such as shrimps, lobsters and crabs (Order Decapoda), and keystone species of aquatic ecosystems such as water fleas (Order Branchiopoda). In terms of decapod sex determination and differentiation, previous approaches have attempted to elucidate their molecular components, to establish mono-sex breeding technology. Here, we overview reports describing the physiological functions of sex hormones regulating masculinization and feminization, and gene discovery by transcriptomics in decapod species. Moreover, this review summarizes the recent progresses of studies on the juvenile hormone-driven sex determination system of the branchiopod genus Daphnia, and then compares sex determination and endocrine systems between decapods and branchiopods. This review provides not only substantial insights for aquaculture research, but also the opportunity to re-organize the current and future trends of this field.

    DOI： 10.3390/genes12020305

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  • Methyl farnesoate regulatory mechanisms underlying photoperiod-dependent sex determination in the freshwater crustacean Daphnia magna. Reviewed International journal

    Kenji Toyota, Tomomi Sato, Taisen Iguchi, Tsuyoshi Ohira

    Journal of applied toxicology : JAT   41 ( 2 )   216 - 223   2021

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    Freshwater zooplankton Daphnia magna has been widely used in ecotoxicology studies. During the last 20 years, it has been demonstrated that the topical application of juvenile hormone (JH) or JH analogs to mother daphnids induce male offspring production. Based on this finding, an in vivo screening validation method for chemicals with JH agonistic effect has developed. Although this screening system successfully identified a number of JH-like chemicals, molecular mechanisms underlying the male sex-determining process remain largely unknown. To address this issue, we established a reliable male- or female-producing system using Daphnia pulex WTN6 strain by changing the rearing photoperiod. Taking advantage of this rearing system, we successfully found several factors involving male sex determination such as ionotropic glutamate receptors, protein kinase C and pantothenate. Here, we used two D. magna strains that can also control the production of female or male offspring by photoperiod differences as model species for ecotoxicology studies. We demonstrated that either treatment of antagonist of ionotropic glutamate receptors or inhibitor of protein kinase C strongly suppressed male offspring production even under male-producing conditions. Moreover, we revealed that male sex-determining processes are likely diverged between D. magna and D. pulex based on the current experiment. This study provides a fine experimental method for in vivo screening not only JH agonists but also JH antagonists. Moreover, using daphnids with photoperiod-dependent sex determination manner will hugely contribute to understanding the mode-of-action of JH in daphnids.

    DOI： 10.1002/jat.4035

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  • Characterization of G protein-coupled estrogen receptors in Japanese medaka, Oryzias latipes. Reviewed International journal

    Kaori Miyaoku, Yukiko Ogino, Anke Lange, Ayaka Ono, Tohru Kobayashi, Masaru Ihara, Hiroaki Tanaka, Kenji Toyota, Hiroshi Akashi, Genki Yamagishi, Tomomi Sato, Charles R Tyler, Taisen Iguchi, Shinichi Miyagawa

    Journal of applied toxicology : JAT   41 ( 9 )   1390 - 1399   2021

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    The G protein-coupled estrogen receptor 1 (Gper1) is a membrane-bound estrogen receptor that mediates non-genomic action of estrogens. A Gper1-mediating pathway has been implicated in reproductive activities in fish, including oocyte growth, but Gper1 has been characterized in only a very limited number of fish species. In this study, we cloned and characterized two genes encoding medaka (Oryzias latipes) Gper1s, namely, Gper1a and Gper1b, and phylogenic and synteny analyses suggest that these genes originate through a teleost-specific whole genome duplication event. We found that Gper1a induced phosphorylation of mitogen-activated protein kinase (MAPK) in 293T cells transfected with medaka Gper1s on exposure to the natural estrogen, 17β-estradiol (E2) and a synthetic Gper1 agonist (G-1), and treatment with both E2 and G-1 also decreased the rate of spontaneous maturation in medaka oocytes. These findings show that the processes for oocyte growth and maturation are sensitive to estrogens and are possibly mediated through Gper1a in medaka. We also show that 17α-ethinylestradiol (EE2), one of the most potent estrogenic endocrine-disrupting chemicals, and bisphenol A (BPA, a weak environmental estrogen) augmented phosphorylation of MAPK through medaka Gper1s in 293T cells. Interestingly, however, treatment with EE2 or BPA did not attenuate maturation of medaka oocytes. Our findings support that Gper1-mediated effects on oocytes are conserved among fish species, but effects of estrogenic endocrine-disrupting chemicals on oocytes acting through Gper1 may be divergent among fish species.

    DOI： 10.1002/jat.4130

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  • Molecular Insights into Structural and Ligand Binding Features of Methoprene-Tolerant in Daphnids. Reviewed International journal

    Masashi Hirano, Kenji Toyota, Hiroshi Ishibashi, Nobuaki Tominaga, Tomomi Sato, Norihisa Tatarazako, Taisen Iguchi

    Chemical research in toxicology   33 ( 11 )   2785 - 2792   2020.11

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    Juvenile hormone (JH) is an important endocrine factor regulating many biological activities in arthropods. In daphnids, methoprene-tolerant (Met) belongs to a basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family protein which has recently been confirmed as a JH receptor and can bind and be activated by JHs and JH agonists. Although the activation of the JH signaling pathway causes many physiological effects, the molecular basis for the structural feature and ligand binding properties of Daphnia Met are not fully understood. To study the ligand preference in terms of structural features of Daphnia Met, we built in silico homology models of the PAS-B domain of Daphnia Mets from cladoceran crustaceans, Daphnia pulex and D. magna. Structural comparison of two Daphnia Met PAS-B domain models revealed that the volume in the main cavity of D. magna Met was larger than that of D. pulex Met. Compared with insect Met, Daphnia Met had a less hydrophobic cavity due to polar residues in the core-binding site. Molecular docking simulations of JH and its analogs with Daphnia Met indicated that the interaction energies were correlated with each of the experimental values of in vivo JH activities based on male induction and in vitro Met-mediated transactivation potencies. Furthermore, in silico site-directed mutagenesis supported experimental findings that Thr292 in D. pulex Met and Thr296 in D. magna Met substitution to valine contribute to JH selectivity and differential species response. This study demonstrates that in silico simulations of Daphnia Met and its ligands may be a tool for predicting the ligand profile and cross species sensitivity.

    DOI： 10.1021/acs.chemrestox.0c00179

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  • Hedgehog signaling regulates the basement membrane remodeling during folliculogenesis in the neonatal mouse ovary. International journal

    Karin J Terauchi, Shinichi Miyagawa, Taisen Iguchi, Tomomi Sato

    Cell and Tissue Research   381 ( 3 )   555 - 567   2020.9

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    In the mouse ovary, interactions between oocytes and somatic cells are essential for folliculogenesis and subsequent follicle development. The polyovular follicle (PF), which contains more than two oocytes in a follicle, can be induced in the neonatal mouse ovary when interactions between oocytes and somatic cells are disrupted by agents such as the potent synthetic estrogen diethylstilbestrol (DES) acting through estrogen receptor (ER) β. Hedgehog signaling is known to regulate granulosa cell proliferation, thecal cell differentiation, and follicle growth. To investigate the role of hedgehog signaling in the early folliculogenesis and in PF induction by DES, neonatal mouse ovaries were cultured with or without 10 μM cyclopamine (CPA), an inhibitor of hedgehog signaling, and grafted under the kidney capsule of adult ovariectomized host mice. The number and the incidence of PFs were significantly increased in organ-cultured ovaries post-grafting. Expression of procollagen type IV, alpha 1 (Col4a1) in organ-cultured ovaries was significantly reduced by CPA, but not by DES. The expression of two hedgehog ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), and a target gene, Hedgehog interacting protein (Hhip), was significantly increased by DES both in WT and ERβ KO mice. Therefore, we infer that DES can affect expression of those genes through ERα but not via suppression of hedgehog signaling. Thus, PFs are induced by DES or CPA, but the induction mechanism is different. Our results revealed an important role of hedgehog signaling in basement membrane remodeling during folliculogenesis even before thecal cell differentiation.

    DOI： 10.1007/s00441-020-03222-9

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  • Diethylstilbestrol alters the expression of activins in the neonatal mouse ovary in vitro. Reviewed

    Oikawa S, S. Kobayashi, S. Miyagawa, T. Iguchi, T. Sato

    In Vivo   33   1095 - 1102   2019

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.21873/invivo.11578

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  • Effects of 2,3-bis(4-hydroxyphenyl)-propionitrile on induction of polyovular follicles in the mouse ovary Reviewed

    Tomomi Sato, Hannah Kim, Hanako Kakuta, Taisen Iguchi

    In Vivo   32 ( 1 )   19 - 24   2018.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Institute of Anticancer Research  

    DOI： 10.21873/invivo.11199

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  • Vagina: Cell biology

    Tomomi Sato, Taisen Iguchi, Sipra Mohapatra

    Encyclopedia of Reproduction   360 - 367   2018.1

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    Language：English   Publishing type：Part of collection (book)   Publisher：Elsevier  

    DOI： 10.1016/B978-0-12-801238-3.64407-0

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  • The involvement of granulosa cells in the regulation by gonadotropins of Cyp17a1 in theca cells. Reviewed

    Kakuta H, T. Iguchi, T. Sato

    In Vivo   32   1387 - 1401   2018

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    DOI： 10.21873/invivo.11391

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  • Photoperiodism of Male Offspring Production in the Water Flea Daphnia pulex. Reviewed

    Kenji Toyota, Tomomi Sato, Norihisa Tatarazako, Taisen Iguchi

    Zoological science   34 ( 4 )   312 - 317   2017.8

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    DOI： 10.2108/zs170005

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  • Establishment of estrogen receptor 1 (ESR1)-knockout medaka: ESR1 is dispensable for sexual development and reproduction in medaka, Oryzias latipes Reviewed

    Saki Tohyama, Yukiko Ogino, Anke Lange, Taijun Myosho, Tohru Kobayashi, Yu Hirano, Gen Yamada, Tomomi Sato, Norihisa Tatarazako, Charles R. Tyler, Taisen Iguchi, Shinichi Miyagawa

    DEVELOPMENT GROWTH & DIFFERENTIATION   59 ( 6 )   552 - 561   2017.8

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    DOI： 10.1111/dgd.12386

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  • Efficacy of Fibroblast Growth Factor on Epithelialization of the Neovagina in Patients with Mayer-Rokitansky-Kuster-Hauser Syndrome Who Underwent Vaginoplasty Reviewed

    Tomoko Nagata, Aiko Kawano, Makiko Koyama, Tomomi Nakamura, Fumiki Hirahara, Tadaaki Nakajima, Tomomi Sato, Hideya Sakakibara

    JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY   30 ( 3 )   400 - 404   2017.6

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    DOI： 10.1016/j.jpag.2015.12.001

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  • Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity. Reviewed International journal

    Kenji Toyota, Timothy D Williams, Tomomi Sato, Norihisa Tatarazako, Taisen Iguchi

    Journal of applied toxicology : JAT   37 ( 3 )   374 - 381   2017.3

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    DOI： 10.1002/jat.3368

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  • Protein kinase C is involved with upstream signaling of methyl farnesoate for photoperiod-dependent sex determination in the water flea Daphnia pulex. Reviewed International journal

    Kenji Toyota, Tomomi Sato, Norihisa Tatarazako, Taisen Iguchi

    Biology open   6 ( 2 )   161 - 164   2017.2

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    DOI： 10.1242/bio.021857

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  • Expression Profile of NOTCH3 in Mouse Spermatogonia Reviewed

    Ryu Okada, Megumi Fujimagari, Eri Koya, Yoshikazu Hirose, Tomomi Sato, Yukio Nishina

    CELLS TISSUES ORGANS   204 ( 5-6 )   283 - 292   2017

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    DOI： 10.1159/000481772

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  • Retinoic acid signaling determines the fate of uterine stroma in the mouse Mullerian duct Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   113 ( 50 )   14354 - 14359   2016.12

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    DOI： 10.1073/pnas.1608808113

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  • Role of Notch signaling in granulosa cell proliferation and polyovular follicle induction during folliculogenesis in mouse ovary Reviewed

    Karin J. Terauchi, Yuri Shigeta, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   365 ( 1 )   197 - 208   2016.7

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    DOI： 10.1007/s00441-016-2371-4

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  • The mechanism and control of Jagged1 expression in Sertoli cells Reviewed

    Ryu Okada, Taro Hara, Tomomi Sato, Nobuhiko Kojima, Yukio Nishina

    REGENERATIVE THERAPY   3   75 - 81   2016.3

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    DOI： 10.1016/j.reth.2016.02.005

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  • Neonatal Estrogen Receptor beta Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus Reviewed

    Tadaaki Nakajima, Yuki Tanimoto, Masami Tanaka, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    ENDOCRINOLOGY   156 ( 9 )   3317 - 3328   2015.9

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    DOI： 10.1210/en.2015-1012

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  • Effects of diethylstilbestrol on luteinizing hormone-producing cells in the mouse anterior pituitary Reviewed

    Machiko Ishikawa, Erina Murai, Yuka Hashiguchi, Taisen Iguchi, Tomomi Sato

    EXPERIMENTAL BIOLOGY AND MEDICINE   239 ( 3 )   311 - 319   2014.3

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    DOI： 10.1177/1535370213519722

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  • Epithelial-stromal Interactions in the Mouse Vagina Exposed Neonatally to Diethylstilbestrol Reviewed

    Tomoko Katoh, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    IN VIVO   27 ( 3 )   333 - 337   2013.5

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  • Cholesterol Homeostasis in the Ovaries of Neonatally Diethylstilbestrol-treated Mice Reviewed

    H. Kakuta, A. Matsushita, K. Arikawa, T. Iguchi, T. Sato

    EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES   121 ( 2 )   94 - 101   2013.2

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    DOI： 10.1055/s-0033-1333780

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  • p21 and Notch Signalings in the Persistently Altered Vagina Induced by Neonatal Diethylstilbestrol Exposure in Mice Reviewed

    Takeshi Nakamura, Shinichi Miyagawa, Yoshinao Katsu, Takeshi Mizutani, Tomomi Sato, Takashi Takeuchi, Taisen Iguchi, Yasuhiko Ohta

    JOURNAL OF VETERINARY MEDICAL SCIENCE   74 ( 12 )   1589 - 1595   2012.12

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    DOI： 10.1292/jvms.12-0182

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  • Sequential Changes in the Expression of Wnt- and Notch-related Genes in the Vagina and Uterus of Ovariectomized Mice after Estrogen Exposure Reviewed

    Takeshi Nakamura, Shinichi Miyagawa, Yoshinao Katsu, Tomomi Sato, Taisen Iguchi, Yasuhiko Ohta

    IN VIVO   26 ( 6 )   899 - 906   2012.11

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  • Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice Reviewed

    Takeshi Nakamura, Shinichi Miyagawa, Yoshinao Katsu, Hajime Watanabe, Takeshi Mizutani, Tomomi Sato, Ken-Ichirou Morohashi, Takashi Takeuchi, Taisen Iguchi, Yasuhiko Ohta

    TOXICOLOGY   296 ( 1-3 )   13 - 19   2012.6

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    DOI： 10.1016/j.tox.2012.02.010

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  • Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse uterus and vagina Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   348 ( 1 )   239 - 247   2012.4

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    DOI： 10.1007/s00441-012-1350-7

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  • Involvement of gonadotropins in the induction of hypertrophy-hyperplasia in the interstitial tissues of ovaries in neonatally diethylstilbestrol-treated mice Reviewed

    Hanako Kakuta, Masami Tanaka, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    REPRODUCTIVE TOXICOLOGY   33 ( 1 )   35 - 44   2012.1

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    DOI： 10.1016/j.reprotox.2011.10.013

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  • The role of fibroblast growth factors on the differentiation of vaginal epithelium of neonatal mice Reviewed

    Tadaaki Nakajima, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    DIFFERENTIATION   82 ( 1 )   28 - 37   2011.7

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    DOI： 10.1016/j.diff.2011.03.005

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  • Involvement of activin signaling in abnormalities of mouse vagina exposed neonatally to diethylstilbestrol Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   344 ( 3 )   527 - 538   2011.6

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    DOI： 10.1007/s00441-011-1161-2

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  • Differential involvement of insulin-like growth factor-I and estrogen on prolactin cells in the mouse anterior pituitary Reviewed

    Tamiki Hikake, Shinji Hayashi, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    EXPERIMENTAL BIOLOGY AND MEDICINE   235 ( 8 )   974 - 980   2010.8

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    DOI： 10.1258/ebm.2010.009396

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  • Involvement of insulin-like growth factor-I for the regulation of prolactin synthesis by estrogen and postnatal proliferation of lactotrophs in the mouse anterior pituitary Reviewed

    Yumi Saitoh, Tamiki Hikake, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   340 ( 1 )   147 - 158   2010.4

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    DOI： 10.1007/s00441-010-0937-0

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  • The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary Reviewed

    Tamiki Hikake, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    JOURNAL OF ENDOCRINOLOGY   203 ( 2 )   231 - 240   2009.11

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    DOI： 10.1677/JOE-09-0232

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  • Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries Reviewed

    Hannah Kim, Tadaaki Nakajima, Shinji Hayashi, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    BIOLOGY OF REPRODUCTION   81 ( 5 )   1002 - 1009   2009.11

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    DOI： 10.1095/biolreprod.108.070599

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  • Involvement of Estrogen Receptor beta in the Induction of Polyovular Follicles in Mouse Ovaries Exposed Neonatally to Diethylstilbestrol Reviewed

    Akiko Kirigaya, Hannah Kim, Shinji Hayashi, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    ZOOLOGICAL SCIENCE   26 ( 10 )   704 - 712   2009.10

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    DOI： 10.2108/zsj.26.704

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  • Effects of diethylstilbestrol on ovarian follicle development in neonatal mice Reviewed

    Hannah Kim, Shinji Hayashi, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    REPRODUCTIVE TOXICOLOGY   27 ( 1 )   55 - 62   2009.1

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    DOI： 10.1016/j.reprotox.2008.10.005

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  • Myostatin and MyoD family expression in skeletal muscle of IGF-1 knockout mice Reviewed

    Masato Miyake, Shinichiro Hayashi, Tomomi Sato, Yoshikazu Taketa, Kouichi Watanabe, Shinji Hayashi, Sachi Tanaka, Shyuichi Ohwada, Hisashi Aso, Takahiro Yamaguchi

    CELL BIOLOGY INTERNATIONAL   31 ( 10 )   1274 - 1279   2007.10

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    DOI： 10.1016/j.cellbi.2007.05.007

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  • Comparison of estrogen responsive genes in the mouse uterus, vagina and mammary gland Reviewed

    Atsuko Suzuki, Hiroshi Urushitani, Hajime Watanabe, Tomomi Sato, Taisen Iguchi, Tomohiro Kobayashi, Yasuhiko Ohta

    JOURNAL OF VETERINARY MEDICAL SCIENCE   69 ( 7 )   725 - 731   2007.7

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    DOI： 10.1292/jvms.69.725

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  • Gene expression change in the Mullerian duct of the mouse fetus exposed to diethylstilbestrol in utero Reviewed

    Atsuko Suzuki, Hiroshi Urushitani, Tomomi Sato, Tomohiro Kobayashi, Hajime Watanabe, Yasuhiko Ohta, Taisen Iguchi

    EXPERIMENTAL BIOLOGY AND MEDICINE   232 ( 4 )   503 - 514   2007.4

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  • Developmental effects of ethinylestradiol on reproductive organs of female mice Reviewed

    Akiko Kirigaya, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    IN VIVO   20 ( 6B )   867 - 873   2006.11

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  • Global gene expression in mouse vaginae exposed to diethylstilbestrol at different ages Reviewed

    A Suzuki, H Watanabe, T Mizutani, T Sato, Y Ohta, T Iguchi

    EXPERIMENTAL BIOLOGY AND MEDICINE   231 ( 5 )   632 - 640   2006.5

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    DOI： 10.1177/153537020623100518

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  • Establishment of a primary culture model of mouse uterine and vaginal stroma for studying in vitro estrogen effects Reviewed

    K Inada, S Hayashi, T Iguchi, T Sato

    EXPERIMENTAL BIOLOGY AND MEDICINE   231 ( 3 )   303 - 310   2006.3

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  • Involvement of growth factors in induction of persistent proliferation of vaginal epithelium of mice exposed neonatally to diethylstilbestrol

    T Sato, Y Fukazawa, Y Ohta, T Iguchi

    REPRODUCTIVE TOXICOLOGY   19 ( 1 )   43 - 51   2004.11

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    DOI： 10.1016/j.reprotox.2004.05.004

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  • Multiple mechanisms are involved in apoptotic cell death in the mouse uterus and vagina induced by ovariectomy.

    Sato T, Fukazawa Y, Kojima H, Ohta Y, Iguchi T

    Reproductive Toxicology   17 ( 289-297 )   2003

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    DOI： 10.1016/S0890-6238(03)00011-X

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  • Bisphenol-A administration during pregnancy results in fetal exposure in mice and monkeys Reviewed

    Kaoru Uchida, Atsuko Suzuki, Yoshio Kobayashi, David Lee Buchanan, Tomomi Sato, Hajime Watanabe, Yoshinao Katsu, Juri Suzuki, Kazuo Asaoka, Chisato Mori, Koji Arizono, Taisen Iguchi

    Journal of Health Science   48 ( 6 )   579 - 582   2002.12

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    DOI： 10.1248/jhs.48.579

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  • The phytoestrogen genistein induces thymic and immune changes: A human health concern? Reviewed

    S Yellayi, A Naaz, MA Szewczykowski, T Sato, JA Woods, JS Chang, M Segre, CD Allred, WG Helferich, PS Cooke

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   99 ( 11 )   7616 - 7621   2002.5

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    DOI： 10.1073/pnas.102650199

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  • Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice. Reviewed

    Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y, Watanabe H, Iguchi T

    Reproductive Toxicology   16 ( 107-116 )   2002

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    DOI： 10.1016/S0890-6238(02)00005-9

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  • Characterization of diethylstilbestrol-induced hypospadias in female mice. Reviewed

    Miyagawa S, Buchanan DL, Sato T, Ohta Y, Nishina Y, Iguchi T

    Anatomical Record   266 ( 43-50 )   2002

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    DOI： 10.1002/ar.10033

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  • Role of systemic and local Insulin-Like Growth Factor I (IGF-I) in the effects of estrogen on growth and epithelial proliferation of mouse uterus. Reviewed

    Sato T, G. Wang, M.P. Hardy, T. Kurita, G.R. Cunha, P.S. Cooke

    Endocrinology   143 ( 2673-2679 )   2673 - 2679   2002

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  • Effect of estrogens on ontogenetic expression of progesterone receptor in the fetal female rat reproductive tract. Reviewed

    Okada A, Ohta Y, Buchanan D, Sato T, Iguchi T

    Molecular and Cellular Endocrinology   195 ( 55-64 )   2002

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    DOI： 10.1016/S0303-7207(02)00211-3

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  • Changes in ontogenetic expression of estrogen receptor alpha and not of estrogen receptor beta in the female rat reproductive tract. Reviewed

    Okada A, Ohta Y, Buchanan DL, Sato T, Inoue S, Hiroi H, Muramatsu M, Iguchi T

    Journal of Molecular Endocrinology   28 ( 87-97 )   2002

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    DOI： 10.1677/jme.0.0280087

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  • Effect of diethylstilbestrol on cell proliferation and expression of epidermal growth factor in the developing female rat reproductive tract

    A Okada, T Sato, Y Ohta, DL Buchanan, T Iguchi

    JOURNAL OF ENDOCRINOLOGY   170 ( 3 )   539 - 554   2001.9

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    DOI： 10.1677/joe.0.1700539

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  • Antiestrogenic effects of 2, 3, 7, 8-Tetrachlorodibenzo-ρ-dioxin in mouse uterus : critical role of the aryl hydrocarbon receptor in stromal tissue.

    BUCHANAN DL

    Toxicological Sciences   57 ( 2 )   302 - 311   2000

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  • Apoptotic cell death in artificially induced deciduoma of pseudopregnant mice

    H Hirabayashi, T Sato, S Kohno, M Tanaka, S Kobayashi, Y Ohta, T Iguchi

    ANATOMICAL RECORD   254 ( 2 )   205 - 213   1999.2

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    DOI： 10.1002/(SICI)1097-0185(19990201)254:2<205::AID-AR6>3.0.CO;2-K

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  • Mode of cell death in the rat metrial gland during peripartum regression

    Y Fukazawa, Y Yamamura, T Sato, T Iguchi, Y Ohta

    ANATOMICAL RECORD   252 ( 3 )   369 - 377   1998.11

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    DOI： 10.1002/(SICI)1097-0185(199811)252:3<369::AID-AR4>3.0.CO;2-4

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  • Apoptotic cell death during the estrous cycle in the rat uterus and vagina

    T Sato, Y Fukazawa, H Kojima, M Enari, T Iguchi, Y Ohta

    ANATOMICAL RECORD   248 ( 1 )   76 - 83   1997.5

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    DOI： 10.1002/(SICI)1097-0185(199705)248:1<76::AID-AR9>3.0.CO;2-D

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  • Apoptosis of pregnancy-dependent mammary tumor and transplantable pregnancy-dependent mammary tumor in mice

    H Kojima, Y Fukazawa, T Sato, M Enari, A Matsuzawa, S Tsunoda, H Nagasawa, Y Ohta, T Iguchi

    CANCER LETTERS   110 ( 1-2 )   113 - 121   1996.12

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    DOI： 10.1016/S0304-3835(96)04469-2

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  • Estrogen receptor (ER) and its messenger ribonucleic acid expression in the genital tract of female mice exposed neonatally to tamoxifen and diethylstilbestrol

    T Sato, Y Ohta, H Okamura, S Hayashi, T Iguchi

    ANATOMICAL RECORD   244 ( 3 )   374 - 385   1996.3

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    DOI： 10.1002/(SICI)1097-0185(199603)244:3<374::AID-AR9>3.0.CO;2-Y

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  • Effect of estrogen on ontogenic expression of progesterone and estrogen receptors in rat uterus

    Y Ohta, Y Fukazawa, T Sato, A Suzuki, N Nishimura, T Iguchi

    ZOOLOGICAL SCIENCE   13 ( 1 )   143 - 149   1996.2

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  • Involvement of the TNF-α system and the Fas system in the induction of apoptosis of mouse mammary glands after weaning

    H. Kojima, Y. Fukazawa, T. Sato, M. Enari, Y. Tomooka, A. Matsuzawa, Y. Ohta, T. Iguchi

    Apoptosis   1 ( 3 )   201 - 208   1996

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    DOI： 10.1007/BF01321103

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  • Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without postpuberal estrogen administration

    K Kamiya, T Sato, N Nishimura, Y Goto, K Kano, T Iguchi

    EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES   104 ( 2 )   111 - 122   1996

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  • INDUCTION OF ESTROGEN-RECEPTOR AND CELL-DIVISION IN GENITAL TRACTS OF MALE-MICE BY NEONATAL EXPOSURE TO DIETHYLSTILBESTROL

    T SATO, A CHIBA, S HAYASHI, H OKAMURA, Y OHTA, N TAKASUGI, T IGUCHI

    REPRODUCTIVE TOXICOLOGY   8 ( 2 )   145 - 153   1994.3

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    DOI： 10.1016/0890-6238(94)90021-3

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  • DEVELOPMENTAL-CHANGES IN MOUSE PLACENTAL CELLS FROM SEVERAL STAGES OF PREGNANCY INVIVO AND INVITRO

    T IGUCHI, N TANI, T SATO, N FUKATSU, Y OHTA

    BIOLOGY OF REPRODUCTION   48 ( 1 )   188 - 196   1993.1

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  • IMMUNOCYTOCHEMICAL LOCALIZATION OF PROGESTERONE-RECEPTOR IN THE REPRODUCTIVE-TRACT OF ADULT FEMALE RATS

    Y OHTA, T SATO, T IGUCHI

    BIOLOGY OF REPRODUCTION   48 ( 1 )   205 - 213   1993.1

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  • MORPHOMETRIC ANALYSIS OF THE PELVIS IN MICE TREATED NEONATALLY WITH TAMOXIFEN

    Y UESUGI, T SATO, T IGUCHI

    ANATOMICAL RECORD   235 ( 1 )   126 - 130   1993.1

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  • Persistent changes in protein synthesis by vagina of ovariectomized mice exposed neonatally to diethylstilbestrol

    Y. Takamatsu, T. Sato, Y. Hayashi, T. Iguchi, N. Takasugi

    In Vivo   7 ( 1 )   97 - 100   1993

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  • Development and mitotic activity of the metrial gland in rat uterus during mid-pregnancy

    Y. Ohta, T. Sato, T. Iguchi

    In Vivo   7 ( 2 )   121 - 126   1993

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  • Estrogen receptor expression in the genital tract of female mice treated neonatally with diethylstilbestrol

    T. Sato, H. Okamura, Y. Ohta, S. Hayashi, Y. Takamatsu, N. Takasugi, T. Iguchi

    In Vivo   6 ( 2 )   151 - 156   1992

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    Language：English   Publishing type：Research paper (scientific journal)  

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  • Developmental pattern of estrogen receptor expression in male mouse genital organs.

    Molecular Andrology.   3   109 - 119   1991

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  • Effect of some hormonally active steroids upon the growth of LNCaP human prostate tumour cells in vitro.

    IGUCHI T.

    Cancer Journal   3   184 - 191   1990

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Books

  • Vagina: Cell Biology, Encyclopedia of Reproduction

    Sato T, T. Iguchi, S. Mohapatra（ Role： Contributor）

    2017 

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  • Handbook of Hormones

    Takei Y, Ando H, Tsutsui K（ Role： Contributor）

    Elsevier  2015 

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  • 2種類のエストロゲンレセプター (ER)：マウス卵巣におけるERベータの機能.

    佐藤 友美（ Role： Sole author）

    横浜市立大学論叢自然科学  2008 

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  • 出生直後のDiethylstilbestrol投与による多卵性卵胞誘導とエストロジェンレセプターβ.

    佐藤 友美（ Role： Joint author）

    日本生殖内分泌学会雑誌  2007 

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MISC

  • レゾルシノールの甲状腺系への内分泌かく乱作用

    井口泰泉, 佐藤友美, 堀江好文

    Endocrine Disrupter News Letter (Web)   23 ( 2 )   2021

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  • New frontiers of developmental endocrinology opened by researchers connecting irreversible effects of sex hormones on developing organs. International journal

    Taisen Iguchi, Tomomi Sato, Tadaaki Nakajima, Shinichi Miyagawa, Noboru Takasugi

    Differentiation; research in biological diversity   2020.10

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    Authorship：Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    In the early 1960's, at Professor Bern's laboratory, University of California, Berkeley) in the US, Takasugi discovered ovary-independent, persistent vaginal changes in mice exposed neonatally to estrogen, which resulted in vaginal cancer later in life. Reproductive abnormalities in rodents were reported as a result of perinatal exposure to various estrogenic chemicals. Ten years later, vaginal cancers were reported in young women exposed in utero to the synthetic estrogen diethylstilbestrol (DES) and this has been called the "DES syndrome". The developing organism is particularly sensitive to developmental exposure to estrogens inducing long-term changes in various organs including the reproductive organs. The molecular mechanism underlying the persistent vaginal changes induced by perinatal estrogen exposure was partly demonstrated. Persistent phosphorylation and sustained expression of EGF-like growth factors, lead to estrogen receptor α (ESR1) activation, and then persistent vaginal epithelial cell proliferation. Agents which are weakly estrogenic by postnatal criteria may have major developmental effects, especially during a critical perinatal period. The present review outlines various studies conducted by four generations of investigators all under the influence of Prof. Bern. The studies include reports of persistent changes induced by neonatal androgen exposure, analyses of estrogen responsive genes, factors determining epithelial differentiation in the Müllerian duct, ESR and growth factor signaling, and polyovular follicles in mammals. This review is then expanded to the studies on the effects of environmental estrogens on wildlife and endocrine disruption in Daphnids.

    DOI： 10.1016/j.diff.2020.10.003

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  • Retinoic acid signaling determines the fate of the uterus from the mouse Müllerian duct. Reviewed

    Nakajima T, T. Sato, T. Iguchi, N. Takasugi

    Reprod. Tox.   86   56 - 61   2019

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1016/j.reprotox.2019.03.006

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  • Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR. Reviewed International journal

    Yukiko Ogino, Saki Tohyama, Satomi Kohno, Kenji Toyota, Gen Yamada, Ryohei Yatsu, Tohru Kobayashi, Norihisa Tatarazako, Tomomi Sato, Hajime Matsubara, Anke Lange, Charles R Tyler, Yoshinao Katsu, Taisen Iguchi, Shinichi Miyagawa

    The Journal of Steroid Biochemistry and Molecular Biology   184   38 - 46   2018.11

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    Sex steroid hormones including estrogens and androgens play fundamental roles in regulating reproductive activities and they act through estrogen and androgen receptors (ESR and AR). These steroid receptors have evolved from a common ancestor in association with several gene duplications. In most vertebrates, this has resulted in two ESR subtypes (ESR1 and ESR2) and one AR, whereas in teleost fish there are at least three ESRs (ESR1, ESR2a and ESR2b) and two ARs (ARα and ARβ) due to a lineage-specific whole genome duplication. Functional distinctions have been suggested among these receptors, but to date their roles have only been characterized in a limited number of species. Sexual differentiation and the development of reproductive organs are indispensable for all animal species and in vertebrates these events depend on the action of sex steroid hormones. Here we review the recent progress in understanding of the functions of the ESRs and ARs in the development and expression of sexually dimorphic characteristics associated with steroid hormone signaling in vertebrates, with representative fish, amphibians, reptiles, birds and mammals.

    DOI： 10.1016/j.jsbmb.2018.06.002

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  • Ecdysteroid and juvenile hormone biosynthesis, receptors and their signaling in the freshwater microcrustacean Daphnia. Reviewed

    Miyakawa H, T. Sato, Y. Song, K.E. Tollefsen, T. Iguchi

    J. Steroid Biochem. Mol. Biol.   184   62 - 68   2018

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1016/j.jsbmb.2017.12.006

    Web of Science

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  • Endocrine disruption and developmental abnormalities of female reproduction

    T Iguchi, T Sato

    AMERICAN ZOOLOGIST   40 ( 3 )   402 - 411   2000.6

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    Language：English  

    Web of Science

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  • 環境ホルモンをさぐる(6)エストロゲン受容体と環境ホルモン

    佐藤 友美, 井口 泰泉

    現代化学   ( 340 )   31 - 42   1999.7

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    Language：Japanese   Publisher：東京化学同人  

    CiNii Books

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  • 内分泌かく乱物質問題について

    佐藤 友美, 井口 泰泉

    横浜市立大学論叢 自然科学系列   50 ( 1 )   129 - 140   1999.3

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    Language：Japanese   Publisher：横浜市立大学学術研究会  

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  • Developmental Expression and Cloning of Estrogen Receptor mRNA in Mummichog, Fundulus heteroclitus(Endocrinology)(Proceedings of the Seventieth Annual Meeting of the Zoological Society of Japan) :

    Urusitani H., Sato T., Iguchi T.

    Zoological science   16   14 - 14   1999

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    Language：English   Publisher：Zoological Society of Japan  

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    Other Link： http://id.nii.ac.jp/1141/00034198/

  • Estrogenic Potencies of Endocrine Disruptors

    IGUCHI Taisen, SATO Tomomi

    46 ( 7 )   571 - 578   1998.7

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  • MOLECULAR CLONING AND TISSUE EXPRESSION OF VASOTOCIN AND MESOTOCIN RECEPTORS FROM THE JAPANESE TREE-FROG

    KOHNO S., FUJIME M., SATO T., KAMISHIMA Y., IGUCHI T.

    13   49 - 49   1998.7

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    Language：English  

    CiNii Books

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  • 5. その他 : a. 環境汚染と生殖

    井口 泰泉, 佐藤 友美

    日本産科婦人科學會雜誌   50 ( 8 )   701 - 712   1998

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    Language：Japanese   Publisher：日本産科婦人科学会  

    CiNii Books

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    Other Link： https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=425059

  • Environmental endocrine disruptors and reproduction.

    Acta Obstet Gynaecology Japan   50   701 - 712   1998

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  • Developmental effects of estrogens and estrogenic compounds in mammals

    T Iguchi, T Sato

    ADVANCES IN COMPARATIVE ENDOCRINOLOGY, TOMES 1 AND 2   1723 - 1728   1997

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    Web of Science

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  • Development effect on gonadal differentiation and bones in Fundulus heteroclitus

    H Urushitani, A Shimizu, Y Fukazawa, T Sato, T Iguchi

    ADVANCES IN COMPARATIVE ENDOCRINOLOGY, TOMES 1 AND 2   311 - 315   1997

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    Language：English  

    Web of Science

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  • Apoptosis detection method.

    Newsletter of Japan Society for Comparative Endocrinology   82 ( 82 )   4 - 8   1996

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    Language：Japanese   Publisher：JAPAN SOCIETY FOR COMPARATIVE ENDOCRINOLOGY  

    DOI： 10.5983/nl2001jsce.22.82_4

    CiNii Books

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  • APOPTOTIC CELL DEATH IN MOUSE UTERUS AND VAGINA INDUCED BY OVARIECTOMY

    SATO Tomomi, FUKAZAWA Yugo, KOJIMA Hiromi, OHTA Yasuhiko, TOMOOKA Yasuhiro, IGUCHI Taisen

    10   49 - 49   1995.10

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  • EPIDERMAL GROWTH-FACTOR RECEPTOR LEVELS IN REPRODUCTIVE-ORGANS OF FEMALE MICE EXPOSED NEONATALLY TO DIETHYLSTILBESTROL

    T IGUCHI, M EDERY, PS TSAI, S OZAWA, T SATO, HA BERN

    PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE   204 ( 1 )   110 - 116   1993.10

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    Web of Science

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  • Estrogen induction of estrogen receptor expression and cell proliferation in mouse reproductive organs.

    43 ( 2 )   115 - 144   1992

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

    CiNii Books

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Presentations

  • 周生期の性ホルモン投与によるマウス雌性生殖腺への影響.

    佐藤 友美

    環境ホルモン学会第23回大会講演会  2010 

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    Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • 性ホルモンおよび内分泌かく乱物質のマウス生殖腺への影響.

    佐藤 友美

    QKKランチョンセミナー  2010 

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    Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • Diethylstilbestrol (DES)投与による多卵性卵胞(PF)誘導とエストロゲンレセプター(ER)bの関与.

    佐藤 友美, 金 翰那, 桐ヶ谷 明子, 井口 泰泉, 林 しん治

    第11回日本生殖内分泌学会学術集会  2006 

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    Presentation type：Oral presentation (general)  

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  • 新生仔期のマウス子宮、膣におけるBMPsの役割.

    佐藤 友美, 中島 忠章, 井口 泰泉

    日本動物学会第80回大会  2009 

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    Presentation type：Poster presentation  

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  • Effects of developmental exposure to endocrine disruptors on female organs of mice. Invited

    SATO Tomomi

    Special Seminar at Hollings Marine Laboratory, Medical University of South Carolina  2015.3 

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  • Effects of developmental exposure to diethylstilbestrol on female reproductive organs of mice. Invited

    SATO Tomomi

    The 63rd NIBB Conference  2015.11 

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    Language：English   Presentation type：Symposium, workshop panel (nominated)  

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  • 性ホルモンおよび内分泌かく乱物質のマウス卵巣への影響と作用機構.

    佐藤 友美

    日本獣医学会第149回大会教育講演  2010 

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  • マウス卵巣における濾胞形成時の顆粒膜細胞増殖と基底膜の変化.

    重田 祐利, 佐藤 友美

    日本動物学会第84回大会  2013 

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  • マウス生殖腺および附属器官の分化・発達機構 Invited

    佐藤 友美

    日本組織細胞化学会第58回学術集会シンポジウム  2017.9 

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Awards

  • 日本生殖内分泌学会平成18年度学術奨励賞

    2006  

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    Country：Japan

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Research Projects

  • The primordial follicle assembly and activation in the neonatal mouse ovary

    Grant number：23K27202  2023.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\18850000 （ Direct Cost: \14500000 、 Indirect Cost：\4350000 ）

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  • The mechanisms of the folliculogenesis in the neonatal mouse ovary

    Grant number：18K06315  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SATO TOMOMI

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    Authorship：Principal investigator  Grant type：Competitive

    A follicle consists of single oocyte and granulosa cells, and it is essential for the female reproduction. Primordial follicles are formed soon after birth, however, the process of folliculogenesis remains unclear. This study is aimed to examine the role of several growth factors in folliculogenesis using the organ-culture system. Activin signaling is involved with early follicle growth, but not folliculogenesis in the neonatal mouse ovary. Inhibition of FGFR showed no effect on follicullogenesis, but it resulted in a suppression of follicle growth. Hedgehog signaling is involved with basement membrane remodeling during folliculogenesis even before thecal cell differentiation. These results provide important information to understand folliculogenesis and early follicle growth in the mouse ovary.

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  • Effects of endocrine disruptors on the HPG axis of neonatal mice

    Grant number：15K07132  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Sato Tomomi

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    Authorship：Principal investigator  Grant type：Competitive

    In the mouse ovary, neonatal exposure to estrogens or endocrine disruptors result in reproductive abnormalities including anovulation, hypertrophy-hyperplasia of the interstitial tissues and induction of polyovular follicles due to the alterations of hypothalamus-pituitary-axis. Our previous reports show that neonatal diethylstilbestrol (DES) exposure causes defeminization in the hypothalamus of female mice, however, the regulation of the pituitary gonadotropins is different from that in male mice. To investigate the effects of neonatal exposure to DES on the hypothalamus, immunohistochemistry of neurokinin B and estrogen receptor α was performed in DES-treated mice. In addition, microarray analysis revealed that neonatal DES treatment induced changes in the gene expression of the hypothalamus.

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  • 生殖機能調節システムに対する性ホルモン様環境化学物質の作用機構の統合的解明

    2012.4 - 2015.3

    学術振興会  2012年度科学研究費補助金 基盤研究(C) 

    佐藤 友美

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    Authorship：Principal investigator  Grant type：Competitive

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  • マウス子宮、膣間質からの上皮細胞分化誘導因子の探索

    Grant number：16770050  2004.4 - 2006.3

    学術振興会  2004年度科学研究費補助金 若手研究(B)  若手研究(B)

    佐藤 友美

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    Authorship：Principal investigator  Grant type：Competitive

    (1)生後2日齢と15日齢のマウス子宮、膣との間でいくつかの遺伝子の発現と局在を調べたところ、子宮ではBMP2,hoxa10,hoxa11の発現が、膣ではBMP4,hoxa13の発現が高かった。またこれらの遺伝子は、主に間質細胞において発現していた。このことは、出生直後のマウス子宮、膣では、形態形成や器官の成長に関与すると思われる遺伝子群がそれぞれ異なって発現していることを示している。さらに、出生直後の合成エストロジェン投与によりいくつかの遺伝子の発現量は有意に減少していた。
    なお、これらの結果はサンディエゴで開催されたアメリカ内分泌学会第87回大会で発表した。
    (2)上皮-間質間相互作用の解析を行うために、マウス子宮、膣間質細胞の初代培養系を確立した。この培養間質細胞はエストロジェン受容体αを発現しており、エストロジェンに反応して細胞増殖が促進される。このとき、細胞増殖を引き起こすエストロジェンの濃度は子宮、膣でそれぞれ異なっていた。このことは、子宮、膣間質細胞におけるエストロジェンに対する反応性が異なっていることを示している。さらに、ビスフェノールAを培地中に加えても細胞増殖が有意に促進されることが明らかとなった。培養間質細胞をマウスの腎臓皮膜下に移植し、宿主にエストロジェンを投与したところ、移植片のDNA合成が促進されたことから、培養間質細胞は生体内でもエストロジェンに反応して増殖することがわかった。さらに、上皮組織と培養間質細胞とを組み合わせて移植すると、正常な子宮、膣に似た組織像を示し、宿主の性周期に依存した上皮の形態変化が見られた。したがって、この培養間質細胞は上皮細胞の増殖を引き起こす能力を保持している事が明らかとなった。(原著論文として発表済み)

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  • 周生期の内分泌攪乱物質投与におけるマウス子宮、膣への影響

    Grant number：14042255  2002.4 - 2003.3

    日本学術振興会  2002年度科学研究費補助金 特定領域研究(A)  特定領域研究

    佐藤 友美

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    Authorship：Principal investigator  Grant type：Competitive

    1.エストロゲンレセプター(ER)によるリガンド依存的な転写調節には、正負それぞれの方向においていくつかの転写共役因子が関わっている。成熟マウスの子宮、膣における、ホルモン投与後のERといくつかの転写共役因子のmRNAの発現変化を調べた。3μgのdiethylstilbestrol(DES)を1回投与すると、子宮、膣のERα,ERβ,SRC-1,GRIP1,SRC-3およびP300のmRNAの発現は減少する傾向を示した。RIP140のmRNA発現はDESを投与して3時間後に一過性に増加し、その後減少した。2mgのbisphenol-A (BPA)を1回投与しても、DESと同様の結果が得られた。以上より、卵巣摘出成熟マウスの子宮、膣において、DESまたはBPA投与によってRIP140の発現が一過性に誘導されることが明らかとなった。このRIP140のmRNAの発現誘導は、DES、BPAともに濃度依存的であった。また、抗RIP140抗体を用いた免疫組織化学法を行ったところ、子宮および膣の上皮において、強い陽性反応を示す細胞が認められた。さらに、DESまたはBPAの1回投与により、間質や平滑筋層で陽性細胞が増加する傾向が見られた。ERαKOマウスにDESまたはBPAを1回投与しても、転写共役因子のmRNA発現には変化はなかった。ERおよび転写共役因子のmRNA発現のパターンがDESとBPA投与とで類似していることから、DESとBPAのマウス生殖器官への作用メカニズムに共通点があることが考えられる。さらにERαKOマウスを用いた実験結果は、DESおよびBPAによる転写共役因子の発現調節にERαが関与していることを強く示唆している。
    2.卵巣摘出後の子宮、膣の退縮は、アポトーシスによるものであり、その際、TNF-αおよびFASが関与していることを明らかにした。

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  • 周生期の内分泌攪乱物質投与におけるマウス膣上皮および間質の相互作用について

    Grant number：13027275  2001.4 - 2002.3

    日本学術振興会  2001年度科学研究費補助金 特定領域研究(A)  特定領域研究(A)

    佐藤 友美

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    Authorship：Principal investigator  Grant type：Competitive

    1.エストロゲンレセプター(ER)によるリガンド依存的な転写調節には、正負それぞれの方向においていくつかの転写共役因子が関わっていることが明らかとなっている。出生直後および成熟マウスの子宮、膣における、ホルモン投与後のERといくつかの転写共役因子のmRNAの発現変化を調べ、器官や時期による違いを比較、検討した。その結果、3μgのジエチルスチルベストロール(DES)を1回投与すると、子宮、膣のERα、ERβ、SRC-1、GRIP1、SRC-3およびp300のmRNAの発現量は減少する傾向を示した。一方、RIP140のmRNAはDESを投与して3時間後に一過性に増加し、その後減少した。出生日のマウスと、2ケ月齢の卵巣摘出マウスの子宮、膣におけるERと転写共役因子のmRNA量を比較したところ、ERαは出生日のマウスにおいて、ERβは卵巣摘出成熟マウスにおいてそれぞれ低かったが、転写共役因子のmRNAの発現量には大きな差は見られなかった。以上の結果をまとめると、子宮、膣における転写共役因子のmRNAの発現量には、時期および器官による差は見られなかったが、DES投与後にRIP140のmRNA発現が一過性に誘導されることが明らかとなった。
    2.エストロゲン刺激によるマウス子宮、膣上皮の細胞増殖、分化は、間質に存在するERαが仲介している。このとき、間質から上皮に向けて分泌される何らかの因子が考えられており、インスリン様成長因子I(IGF-I)もその候補の一つとして挙げられている。IGF-Iノックアウトマウスの生殖器官は未成熟だが、その子宮を正常マウスの腎臓皮膜下に移植したところ、エストロゲンに対して正常に反応することが明らかとなった。このことから、従来考えられていたエストロゲン刺激によって間質でIGF-Iがつくられ、それが上皮に作用するという経路は必ずしも必要ではないことが示唆された。

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  • Developmental Effect of Endocrine Disruptors on Fish and Mice

    Grant number：11839022  1999 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    IGUCHI Taisen, KATSU Yoshinao

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    Grant amount：\4100000 （ Direct Cost: \4100000 ）

    Bisphenol-A (BPA), an estrogenic chemical, was given to pregnant mice and Japanese monkey and studied transplacental transfer. BPA was foun in fetal brain, liver and other organs in 30 min in mice and 1 h in monkey suggesting that BPA can be easily cross the placenta. BPA and a synthetic estrogen, diethylstilbestrol (DES), were given to pregnant mice and studied fertility and various abnormalities in female offspring. DES induced sterility, polyovular follicles in ovary and persistent stratification of vaginal epithelium, but not BPA.Hoxa-9 and a-10 genes in Mullerian duct were downregulated by DES in the fetal period suggesting the close correlation to uterine changes in DES-exposed mice. In order to study low dose issue of BPA, 2 and 20μg/kg body weight of BPA and 0.02-2μg/kg of DES were given to day 10 to 17 of pregnancy. In 20μg BPA-and all DES-exposed female offspring showed significantly early vaginal opening and lower body weight as compared to controls. This results suggest that there is a low dose effect of BPA, however, the mechanism underlie is still unclear. Neonatal DES treatment induced hypospadias in female mice, fusion of urethra and vaginal lumen at lower position of vagina, where apoptosis was observed. The critical period in induction of hypospadias was 7 days after birth. Neonatally BPA (150μg) treated female mice showed persistent estrus, and ovary-independent vaginal changes.
    In order to study estrogenic agents on development of fish, Fundulus heteroclitus embryos were exposed to estradiol. Various malformations, including sex ratio change were induced by estradiol. Estrogen receptor α and β were cloned and ER expression during development were analysed. FTZ-F1 gene was also cloned from Fundulus. In zebrafish, gonad develops to ovary by ca 20 days after hatching then a half of fish develop testis from the ovary. During testis formation, apoptosis of oocytes occurred in the ovary.

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