Molecular mechanisms of ovarian differentiation induced by sex hormones

• Project/Area Number: 20247004
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: Ehime University (2011); National Institute for Basic Biology (2008-2010)
• Principal Investigator: NAGAHAMA Yoshitaka 愛媛大学, 南予水産研究センター, 教授 (50113428)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥48,880,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥11,280,000); Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000); Fiscal Year 2009: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2008: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 卵巣分化 / エストロゲン/エストロゲン受容体 / R-spondin1 / 減数分裂開始 / 魚類 / 遺伝子ノックダウン(RNAi) / C21 steroid / 17α,20β-ジヒドロキシ-4-プレグネン-3-オン(DHP) / エストロゲン / エストロゲン受容体 / RNAi / tilling / メダカ / 性転換 / R-spondinl / C21ステロイド / 7α / 20β-ジヒドロキシ-4-プレグネン-3-オン / Meiosis / Mitosis / ティラピア / チトクロームP450c17

Research Abstract

Molecular mechanisms of sex hormone-induced ovarian differentiation were investigated in two fishes (medaka and tilapia). Our results show that estrogen (E2) induces ovarian differentiation by acting through estrogen receptors (β2 and β1) and R-spondin1. We also suggest that P450c17-II (a steroidogenic enzyme necessary for the production of DHP, maturation-inducing hormone of fish) is involved in the initiation of meiosis in both XX and XY fish.

Research Products

• [Journal Article] R-spondins are involved in the ovarian differentiation in a teleost, medaka (Oryzias latipes) (2012)
  • Author(s): Zhu, L.Y., Wang, D.S., Charkraborty, T., Mohapatra, S. and Nagahama, Y
  • Journal Title: BMC Dev. Biol. Volume: 12 Issue: 1 Pages: 36-36
  • DOI: 10.1186/1471-213x-12-36
  • Peer Reviewed
• [Journal Article] The forkhead gene family in medaka : expression patterns and gene evolution. Cytogenet (2012)
  • Author(s): Shen, X., Cui, J. and Nagahama Y
  • Journal Title: Genome Res. Volume: 136 Issue: 2 Pages: 123-130
  • DOI: 10.1159/000335898
  • Peer Reviewed
• [Journal Article] Expression patterns of gonadotropin hormones and their receptors during early sexual differentiation in Nile tilapia Oreochromis niloticus (2012)
  • Author(s): Yan, H., Ijiri, S., Wu, Q., Kobayashi, T., Li, S., Nakaseko, T., Adachi, S. and Nagahama, Y
  • Journal Title: Biol. Reprod Volume: 87 Issue: 5 Pages: 116-126
  • DOI: 10.1095/biolreprod.112.101220
  • Peer Reviewed
• [Journal Article] Expression of 3β-hydroxysteroid dehydrogenase (hsd3b), star and ad4bp/sf-1 during gonadal development in medaka (Oryzias latipes) (2012)
  • Author(s): Nakamoto, M., Fukasawa, M., Tanaka, S., Shimamori, K., Suzuki, A., Matsuda, M., Kobayashi, T., Nagahama, Y., Shibata, N.
  • Journal Title: Gen Comp Endocrinol Volume: 176 Issue: 2 Pages: 222-30
  • DOI: 10.1016/j.ygcen.2012.01.019
  • Peer Reviewed
• [Journal Article] Dmrt1 mutation causes a male-to-female sex reversal after the sex determination by Dmy in the medaka (2011)
  • Author(s): Masuyama H, Yamada M, Kamei Y, Fujiwara-Ishikawa T, Todo T, Nagahama Y, Matsuda M
  • Journal Title: Chromosome Res Volume: 20(1) Issue: 1 Pages: 163-76
  • DOI: 10.1007/s10577-011-9264-x
  • Peer Reviewed
• [Journal Article] Exposure to diethylstilbesterol during embryonic and larval stages of medaka fish (Oryzias latipes) leads to sex reversal in genetic males and reduced gonad weight in genetic females (2011)
  • Author(s): Paul-Prasanth, B., Shibata, Y., Horiguchi, R. and Nagahama, Y
  • Journal Title: Endocrinology Volume: 115 Issue: 2 Pages: 707-717
  • DOI: 10.1210/en.2010-0812
  • Peer Reviewed
• [Journal Article] Differential expression of three estrogen receptor subtype mRNAs in gonads and liver from embryos to adults of the medaka, Oryzias latipes (2011)
  • Author(s): Charkraborty, T., Shibata, Y., Zhou, L.Y., Katsu, Y., Iguchi, T. and Nagahama, Y
  • Journal Title: Mol. Cell. Endocrinol Volume: 333 Issue: 1 Pages: 47-54
  • DOI: 10.1016/j.mce.2010.12.002
  • Peer Reviewed
• [Journal Article] Estrogen receptors in medaka (Oryzias latipes) and estrogenic environmental contaminants : An in vitro-in vivo correlation (2011)
  • Author(s): Charkraborty, T., Katsu, Y., Zhou, L.Y., Miyagawa, S., Nagahama, Y. and Iguchi, T
  • Journal Title: J. Steroid Biochem. Mol. Biol. Volume: 123 Issue: 3-5 Pages: 115-121
  • DOI: 10.1016/j.jsbmb.2010.11.015
  • Peer Reviewed
• [Journal Article] Exposure to diethylstilbesterol during embryonic and larval stages of medaka fish (Oryzias latipes) leads to sex reversal in genetic males and reduced gonad weight in genetic females (2011)
  • Author(s): Paul-Prasanth, B., Shibata, Y., Horiguchi, R., Nagahama, Y.
  • Journal Title: Endocrinology 152 Pages: 707-717
  • Peer Reviewed
• [Journal Article] Differential expression of three estrogen receptor subtype mRNAs in gonads and liver from embryos to adults of the medaka, Oryzias latipes (2011)
  • Author(s): Charkraborty, T., Shibata, Y., Zhou, L.Y., Katsu, Y., Iguchi, T., Nagahama, Y.
  • Journal Title: Mol.Cell.Endocrinol. 333 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Estrogen receptors in medaka (Oryzias latipes) and estrogenic environmental contaminants : An in vitro-in vivo correlation (2011)
  • Author(s): Charkraborty, T., Katsu, Y., Zhou, L.Y., Miyagawa, S., Nagahama, Y., Iguchi, T.
  • Journal Title: J.Steroid Biochem.Mol.Biol. 123 Pages: 115-121
  • Peer Reviewed
• [Journal Article] Differential expression of three estrogen receptor subtype mRNAs in gonads and liver from embryos to adults of the medaka, Oryzias latipes. (2011)
  • Author(s): Charkraborty, T., Shibata, Y., Zhou, L.Y., Katsu, Y., Iguchi, T., Nagahama, Y.
  • Journal Title: Molecular and Cellular Endocrinology Volume: 333 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Exposure to diethylstilbesterol during embryonic and larval stages of medaka fish (Oryzias latipes) leads to sex reversal in genetic males and reduced gonad weight in genetic females. (2011)
  • Author(s): Paul-Prasanth, B., Shibata, Y., Horiguchi, R., Nagahama, Y.
  • Journal Title: Endocrinology Volume: 152 Pages: 707-717
  • Peer Reviewed
• [Journal Article] Cloning and expression of medaka cholesterol side chain cleavage cytochrome P450 during gonadal development. Develop (2010)
  • Author(s): Nakamoto, M., Fukasawa, M., Orii, S., Shimamori, K., Maeda, T., Suzuki, A., Matsuda, M., Kobayashi, T., Nagahama, Y. and Shibata, N
  • Journal Title: Growth Differ Volume: 52 Issue: 4 Pages: 385-395
  • DOI: 10.1111/j.1440-169x.2010.01178.x
  • Peer Reviewed
• [Journal Article] Doublesex- and mab-3-Related transcription factor-1 repression of aromatase transcription, a possible mechanism favoring the male pathway in tilapia (2010)
  • Author(s): Wang, D.S., Zhou, L.Y., Kobayashi, T., Matsuda, M., Shibata, Y., Sakai, F. and Nagahama, Y
  • Journal Title: Endocrinology Volume: 151 Issue: 3 Pages: 1331-1340
  • DOI: 10.1210/en.2009-0999
  • Peer Reviewed
• [Journal Article] Cloning and expression of medaka cholesterol side chain cleavage cytochrome P450 during gonadal development. (2010)
  • Author(s): Nakamoto, M., Fukasawa, M., Orii, S., Shimamori, K., Maeda, T., Suzuki, A., Matsuda, M., Kobayashi, T., Nagahama, Y., Shibata, N.
  • Journal Title: Development, Growth and Differentiation Volume: 52 Pages: 385-395
  • NAID: 10027564905
  • Peer Reviewed
• [Journal Article] Homologymodeled ligand-binding domains of medaka estrogen receptors and androgen receptors : a model system for the study of reproduction. Biochem (2009)
  • Author(s): Cui, J.Z., Shen, X.Y., Yan, Z.W., Zhao, H.B. and Nagahama, Y
  • Journal Title: Biophys. Res. Comm. Volume: 380 Issue: 1 Pages: 115-121
  • DOI: 10.1016/j.bbrc.2009.01.047
  • Peer Reviewed
• [Journal Article] Gonadal sex differentiation and expression of Sox9a2, Dmrt1, and Foxl2 in Oryzias luzonensis (2009)
  • Author(s): Nakamoto, M., Muramatsu, S., Yoshida, S., Matsuda, M., Nagahama, Y. and Shibata, N
  • Journal Title: Genesis Volume: 47 Issue: 5 Pages: 289-299
  • DOI: 10.1002/dvg.20498
  • Peer Reviewed
• [Journal Article] Molecular aspects of gonadal differentiation in a teleost fish, the Nile tilapia (2009)
  • Author(s): Kobayashi, T. and Nagahama, Y
  • Journal Title: Sex. Dev. Volume: 3 Issue: 2-3 Pages: 108-117
  • DOI: 10.1159/000223076
  • Peer Reviewed
• [Journal Article] Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen receptors : a model system for the study of reproduction (2009)
  • Author(s): Cui, J.Z., Shen, X.Y., Yan, Z.W., Zhao, H.B., Nagahama, Y.
  • Journal Title: Biochem.Biophys.Res.Comm. 380 Pages: 115-121
  • Peer Reviewed
• [Journal Article] Gonadal sex differentiation and expression of Sox9a2, Dmrt1, and Foxl2 in Oryzias luzonensis (2009)
  • Author(s): Nakamoto, M., Muramatsu, S., Yoshida, S., Matsuda, M., Nagahama, Y., Shibata, N.
  • Journal Title: Genesis 47 Pages: 289-299
  • Peer Reviewed
• [Journal Article] Molecular aspects of gonadal differentiation in a teleost fish, the Nile tilapia (2009)
  • Author(s): Kobayashi, T., Nagahama, Y.
  • Journal Title: Sex.Dev. 3 Pages: 108-117
  • Peer Reviewed
• [Journal Article] Gonadal sex differentiation and expression of Sox9a2, Dmrt1, and Foxl2 in Oryzias luzonensis 1 (2009)
  • Author(s): Nakamoto, M., Muramatsu, E., Yoshida, S., Matsuda, M., Nagahama, Y., Shibata, N.
  • Journal Title: Genesis 47 Pages: 289-299
  • Peer Reviewed
• [Journal Article] Molecular aspects of gonadal differentiation in a teleost fish, the Nile tilapia (2009)
  • Author(s): Kobayashi, T., Nagahama, Y.
  • Journal Title: Sexual Development 3 Pages: 108-117
  • Peer Reviewed
• [Journal Article] Duplication and distinct expression patterns of two thrombospondin-1 Isoforms in teleost fishes (2009)
  • Author(s): Wu, F.R, Zhou, L.Y., Nagahama, Y., Wang, D.S.
  • Journal Title: Gene Expression Patterns 9 Pages: 436-443
  • Peer Reviewed
• [Journal Article] Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen receptors : a model system for the study of reproduction (2009)
  • Author(s): Cui, J. Z., Shen, X. Y., Yan, Z. W., Zhao, H. B., Nagahama, Y.
  • Journal Title: Biochem. Biophys. Res. Comm. 380 Pages: 115-121
  • Peer Reviewed
• [Presentation] Genetic and hormonal regulation of gonadal development and sexual plasticity in fish (2013)
  • Author(s): Nagahama, Y
  • Organizer: 2013 Society for Integrative and Comparative Biology (SICB) Annual Meeting
  • Place of Presentation: San Francisco CA, USA (Invited lecture)
• [Presentation] 魚類の性決定・分化と性的可塑性の分子メカニズム (2012)
  • Author(s): 長濱嘉孝
  • Organizer: 日本動物学会第83回大会シンポジウム
  • Place of Presentation: 大阪大学, 大阪
• [Presentation] 魚類の卵成熟誘起機構 (2012)
  • Author(s): 柴田安司, 成瀬清, 長濱嘉孝
  • Organizer: 日本動物学会中部支部大会
  • Place of Presentation: 松本
• [Presentation] Sex determination/differentiation and sexual plasticity in fish (2011)
  • Author(s): Nagahama, Y.
  • Organizer: Cold Spring Harbor Asia Conferences
  • Place of Presentation: Suzhou, China(招待講演)
  • Year and Date: 2011-10-11
• [Presentation] Transgenerational knockdown of DMY in medaka, Oryzias latipes (2011)
  • Author(s): Chakraborty.T., Zhou, L.Y., Iguchi T., Nagahama, Y.
  • Organizer: 9th International Symposium on Reproductive Physiology of Fish
  • Place of Presentation: Cochin, India
  • Year and Date: 2011-08-14
• [Presentation] Ovarian estrogens are critical for the suppression of male sexual behavior in adult female Japanese medaka, Oryzias latipes (2011)
  • Author(s): Paul-Prasanth, B., Nagahama, Y.
  • Organizer: 9th International Symposium on Reproductive Physiology of Fish
  • Place of Presentation: Cochin, India
  • Year and Date: 2011-08-10
• [Presentation] Sex determination/differentiation and sexual plasticity in fish (2011)
  • Author(s): Nagahama, Y.
  • Organizer: The inaugural meeting of the North American Society for Comparative Endocrinology (NASCE 2011)
  • Place of Presentation: University of Michigan (Ann Arbor, USA)(招待講演)
  • Year and Date: 2011-07-14
• [Presentation] Gene expression profiling of ovarian follicles in medaka, Oryzias latipes (2011)
  • Author(s): Shibata, Y., Nagahama, Y., Young, G. and Naruse, K
  • Organizer: Center for Reproductive Biology, 15th Annual Retreat
  • Place of Presentation: Washington State University, Pullman, WA, USA
  • Year and Date: 2011-05-19
• [Presentation] Gene expression profiling of ovarian follicles in medaka, Oryzias latipes (2011)
  • Author(s): Shibata, Y., Nagahama.Y., Young, G., Naruse, K.
  • Organizer: The 15^<th> Annual Retreat, Center for Reproductive Biology
  • Place of Presentation: Pullman, USA
  • Year and Date: 2011-05-19
• [Presentation] Sex determination/ differentiation and sexual plasticity in fish (2011)
  • Author(s): Nagahama, Y
  • Organizer: The Inaugural Meeting of the North American Society for Comparative Endocrinology
  • Place of Presentation: University of Michigan, Ann Arbor, MI, USA (Invited lecture)
• [Presentation] Sex determination/ differentiation and sexual plasticity in fish (2011)
  • Author(s): Nagahama, Y
  • Organizer: Cold Spring Harbor Asia Conference on Developmental Control of Sex, Growth and Cellular Fate
  • Place of Presentation: Suzhou, China (Invited lecture)
• [Presentation] Sex determination and sexual plasticity in fish (2010)
  • Author(s): Nagahama, Y
  • Organizer: Satellite International Symposium on Reproductive Biology of Aquatic Organisms
  • Place of Presentation: Motobu-cho, Okinawa, Japan (Invited lecture)
  • Year and Date: 2010-06-30
• [Presentation] Sex determination and Sexual Plasticity in Fish. (2010)
  • Author(s): Nagahama, Y.
  • Organizer: Satellite International Symposium on Reproduction Biology of Aquatic Organisms-Researches from the Tropical to Temperate Zone.
  • Place of Presentation: Motobu, Okinawa, Japan.
  • Year and Date: 2010-06-30
• [Presentation] Sex determination in fish (2010)
  • Author(s): Yoshitaka Nagahama
  • Organizer: Howard Bern Symposium : Recent Advances in Comparative Endocrinology
  • Place of Presentation: Berkeley, California, USA
  • Year and Date: 2010-03-02
• [Presentation] Sex determination in fish (2010)
  • Author(s): Nagahama, Y
  • Organizer: Howard Bern Symposium: Recent Advances in Comparative Endocrinology
  • Place of Presentation: Berkeley, CA, USA (Invited lecture)
• [Presentation] Sex determination and sexual plasticity in fish (2010)
  • Author(s): Nagahama, Y.
  • Organizer: Satellite International Symposium in Reproductive Biology of Aquatic Organisms-Researches from the Tropical to Temperate Zone
  • Place of Presentation: Motobu, Okinawa, Japan.
• [Presentation] Sex determination (2010)
  • Author(s): Nagahama, Y.
  • Organizer: Howard Bern Symposium : Recent Advances in Comparative Endocrinology
  • Place of Presentation: Berkeley, California, USA.
• [Presentation] R-spondin1 is essential for ovarian differentiation in fish (2009)
  • Author(s): Zhou, L.Y., T. Chakraborty, Wang, D.S. and Nagahama, Y
  • Organizer: 16th International Congress of Comparative Endocrinology
  • Place of Presentation: University of Hong Kong, Hong Kong
  • Year and Date: 2009-06-23
• [Presentation] Sexual plasticity in fish (2009)
  • Author(s): Yoshitaka Nagahama
  • Organizer: Fifth International Symposium on the Biology of vertebrate sex determination(Opening lecture)
  • Place of Presentation: Kona, Hawaii, USA
  • Year and Date: 2009-04-21
• [Presentation] Sexual plasticity in fish (2009)
  • Author(s): Nagahama, Y
  • Organizer: Fifth International Symposium on the Biology of Vertebrate Sex Determination
  • Place of Presentation: Kona, Hawaii, USA (Opening lecture)
• [Presentation] Sexual plasticity in fish (2009)
  • Author(s): Nagahama, Y.
  • Organizer: Fifth International Symposium on the Biology of Vertebrate Sex Determination (Opening Lecture)
  • Place of Presentation: Kona, Hawaii, USA.
• [Presentation] Mechanisms of sex determination/differentiation and sexual plasticity in fish (2008)
  • Author(s): Nagahama, Y
  • Organizer: 2nd International SOX meeting
  • Place of Presentation: Awaji, Japan (Special lecture)
• [Presentation] Sex determination/ differentiation and sexual plasticity in fish (2008)
  • Author(s): Nagahama, Y
  • Organizer: International Symposium for Gonad and Brain Sex Differentiation
  • Place of Presentation: Fukuoka, Japan (Invited lecture)
• [Presentation] Sex determination/ differentiation and sexual plasticity in fish (2008)
  • Author(s): Nagahama, Y
  • Organizer: XXth International Congress of Zoology
  • Place of Presentation: Paris, France (Invited lecture)
• [Presentation] Expression of a lyasedeficient Cyp17 in the fish head kidney (2008)
  • Author(s): Nagahama, Y.
  • Organizer: XIIIth International Conference on the Adrenal Cortex
  • Place of Presentation: San Francisco, CA, USA (Invited lecture)
• [Presentation] Sex determination, differentiation and sexual plasticity in fish: Current status and future directions (2008)
  • Author(s): Nagahama, Y
  • Organizer: International Symposium on Sex Determination and Gametogenesis in Fish: Current Status and Future Directions
  • Place of Presentation: University of Hawaii, Honolulu, Hawaii, USA (Special lecture)
• [Presentation] Sexual plasticity in fish (2008)
  • Author(s): Nagahama, Y
  • Organizer: The 54th NIBB Conference on New Frontiers for the Medaka Model Genome
  • Place of Presentation: Okazaki, Japan (Invited lecture)
• [Presentation] 魚類の性決定・性分化とステロイドホルモン (2008)
  • Author(s): 長濱嘉孝
  • Organizer: 日本動物学会第79回大会シンポジウム
  • Place of Presentation: 福岡大学, 福岡
• [Presentation] 魚類の性決定・性分化とステロイドホルモン (2008)
  • Author(s): 長濱嘉孝
  • Organizer: 日本動物学会第79回大会シンポジウム
  • Place of Presentation: 福岡
• [Book] Diversity and plasticity of sex determination and differentiation in fishes. In "Control of Gonadal Development" (Jimenez, R. Ed.) (2012)
  • Author(s): Kobayashi, Y., Nagahama, Y. and Nakamura, M
  • Publisher: Karger(In press)
• [Book] Endocrine regulation of oogenesis in the medaka, Oryzias latipes. In "Medaka : A Model for Organogenesis, Human Disease and Evolution" (H. Takeda et al. eds. (2011)
  • Author(s): Shibata, N., Nakamoto, M., Shibata, Y. and Nagahama, Y.
  • Publisher: Springer
• [Book] Sex determination in fishes(Vol.1)("Hormones and Reproduction of Vertebrates") (2011)
  • Author(s): Paul-Prasanth, B., Nakamura, M., Nagahama, Y.
• [Book] In "Hormones and Reproduction of Vertebrates" Vol.1 (2011)
  • Author(s): Paul-Prasanth, B., Nakamura, M., Nagahama, Y.
  • Total Pages: 14
  • Publisher: Sex determination in fishes.
• [Book] Sex determination in fishes. In "Hormones and Reproduction of Vertebrates" Vol. 1 (D.O. Norris, and K.H. Lopez eds.) (2010)
  • Author(s): Paul-Prasanth, B., Nakamura, M. and Nagahama, Y.
  • Publisher: Academic Press