Endocrine and Environmental Control of Sex Differentiation in Gonochoristic Fish

Part of the Diversity and Commonality in Animals book series (DCA)


Sex in vertebrates, including fish, is usually determined by genotype. In medaka (Oryzias latipes), a gonochoristic fish with the XX/XY sex determination system, a gene that encodes the DM domain on the Y chromosome is identified as the master sex-determining gene. However, the sex-determining genes in many nonmammalian vertebrates remain unclarified. In contrast, sex determination in some reptiles, amphibians, and fish is influenced greatly by environmental factors. For example, although the genotypic sex determination mechanism in Japanese flounder (Paralichthys olivaceus) is basically the XX/XY type, genotypic females can be sex reversed to phenotypic males by rearing the larvae at high or low water temperatures during gonadal sex differentiation. In addition, the phenotypic sex of many teleost fish, including flounder, can be experimentally altered by treatment with sex steroid hormones, suggesting an important role for sex steroid hormones in gonadal sex differentiation in fish. In this chapter, we review general information and recent knowledge on the basic mechanisms of sex determination and gonadal sex differentiation, and present the effects of sex steroid hormones and water temperature on gonadal sex differentiation in gonochoristic fish.


Gonadal sex differentiation Temperature-dependent sex determination Estrogen Androgen Medaka Japanese flounder Gonochoristic fish 


  1. Adkins-Regan E (1987) Hormones and sexual differentiation. In: Norris DO, Jones RE (eds) Hormones and reproduction in fishes, amphibians and reptiles. Plenum Press, New York, pp 1–29Google Scholar
  2. Aida T (1921) On the inheritance of colour in a freshwater fish, Aplocheilus latipes Temminck and Schlegel, with special reference to sex-linked inheritance. Genetics 6:554–573Google Scholar
  3. Ashby KR (1957) The effect of steroid hormones on the brown trout (Salmo trutta L.) during the period of gonadal differentiation. J Embryol Exp Morphol 5:225–249Google Scholar
  4. Baroiller JF, Chourrout D, Fostier A, Jalabert B (1995) Temperature and sex chromosomes govern sex ratios of mouthbrooding cichlid fish Oreochromis niloticus. J Exp Zool 273:216–223Google Scholar
  5. Bulmer M (1987) Sex determination in fish. Nature 326:440–441CrossRefPubMedGoogle Scholar
  6. Carragher JF, Sumpter JP (1990) The effect of cortisol on the secretion of sex steroids from cultured ovarian follicles of rainbow trout. Gen Comp Endocrinol 77:403–407CrossRefPubMedGoogle Scholar
  7. Çek S (2006) Early gonadal development and sex differentiation in rosy barb (Puntius conchonius). Anim Biol 56:335–350Google Scholar
  8. Conover DO, Heins SW (1987) Adaptive variation in environmental and genetic sex determination in a fish. Nature 326:496–498CrossRefPubMedGoogle Scholar
  9. Conover DO, Kynard BE (1981) Environmental sex determination: interaction between temperature and genotype in a fish. Science 213:577–579CrossRefPubMedGoogle Scholar
  10. Desprez D, Mélard C (1998) Effect of ambient water temperature on sex determination in the blue tilapia Oreochromis aureus. Aquaculture 162:79–84Google Scholar
  11. Essenberg JM (1923) Sex differentiation in the viviparous teleost Xiphophorus helleri Heckel. Biol Bull 45:46–96Google Scholar
  12. Gimeno S, Gerritsen A, Bowmer T, Komen H (1996) Feminization of male carp. Nature 384:221–222CrossRefPubMedGoogle Scholar
  13. Guiguen Y, Baroiller JF, Ricordel MJ, Iseki K, McMeel OM, Martin SAM, Fostier A (1999) Involvement of estrogens in the process of sex differentiation in two fish species: the rainbow trout (Oncorhynchus mykiss) and a tilapia (Oreochromis niloticus). Mol Reprod Dev 54:154–162Google Scholar
  14. Hattori RS, Gould RJ, Fujioka T, Saito T, Kurita J, Strüussmann CA, Yokota M, Watanabe S (2007) Temperature-dependent sex determination in Hd-rR medaka Oryzias latipes: gender sensitivity, thermal threshold, critical period, and DMRT1 expression profile. Sex Dev 1:138–146Google Scholar
  15. Hayashi Y, Kobira H, Yamaguchi T, Shiraishi E, Yazawa T, Hirai T, Kamei Y, Kitano T (2010) High temperature causes masculinization of genetically female medaka by elevation of cortisol. Mol Reprod Dev 77:679–686CrossRefPubMedGoogle Scholar
  16. Hsueh AJ, Erickson GF (1978) Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells. Steroids 32:639–648CrossRefPubMedGoogle Scholar
  17. Hunter GA, Donaldson EM (1987) Hormonal sex control and its application to fish culture. In: Hoar WS, Randall DJ, Donaldson EM (eds) Fish physiology, vol 6b. Academic, New York, pp 223–291Google Scholar
  18. Ijiri S, Kaneko H, Kobayashi T, Wang DS, Sakai F, Paul-Prasanth B, Nakamura M, Nagahama Y (2008) Sexual dimorphic expression of genes in gonads during early differentiation of a teleost fish, the Nile tilapia Oreochromis niloticus. Biol Reprod 78:333–341Google Scholar
  19. Imai T, Saino K, Matsuda M (2015) Mutation of gonadal soma-derived factor induces medaka XY gonads to undergo ovarian development. Biochem Biophys Res Commun 467:109–114CrossRefPubMedGoogle Scholar
  20. Ishikawa Y (2000) Medakafish as a model system for vertebrate developmental genetics. BioEssays 22:487–495CrossRefPubMedGoogle Scholar
  21. Kaneko H, Ijiri S, Kobayashi T, Izumi H, Kuramochi Y, Wang D, Mizuno S, Nagahama Y (2015) Gonadal soma-derived factor (gsdf), a TGF-beta superfamily gene, induces testis differentiation in the teleost fish Oreochromis niloticus. Mol Cell Endocrinol 415:87–99Google Scholar
  22. Kitano T, Takamune K, Kobayashi T, Nagahama Y, Abe S (1999) Suppression of P450 aromatase gene expression in sex-reversed males produced by rearing genetically female larvae at a high water temperature during a period of sex differentiation in the Japanese flounder (Paralichthys olivaceus). J Mol Endocrinol 23:167–176Google Scholar
  23. Kitano T, Takamune K, Nagahama Y, Abe S (2000) Aromatase inhibitor and 17α-methyltestosterone cause sex-reversal from genetical females to phenotypic males and suppression of P450 aromatase gene expression in Japanese flounder (Paralichthys olivaceus). Mol Reprod Dev 56:1–5Google Scholar
  24. Kitano T, Yoshinaga N, Shiraishi E, Koyanagi T, Abe S (2007) Tamoxifen induces masculinization of genetic females and regulates P450 aromatase and Müllerian inhibiting substance mRNA expression in Japanese flounder (Paralichthys olivaceus). Mol Reprod Dev 74:1171–1177Google Scholar
  25. Kitano T, Hayashi Y, Shiraishi E, Kamei Y (2012) Estrogen rescues masculinization of genetically female medaka by exposure to cortisol or high temperature. Mol Reprod Dev 79:719–726CrossRefPubMedGoogle Scholar
  26. Kobayashi T, Kajiura-Kobayashi H, Nagahama Y (2003) Induction of XY sex reversal by estrogen involves altered gene expression in a teleost, tilapia. Cytogenet Genome Res 101:289–294CrossRefPubMedGoogle Scholar
  27. Kobayashi T, Matsuda M, Kajiura-Kobayashi H, Suzuki A, Saito N, Nakamoto M, Shibata N, Nagahama Y (2004) Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes. Dev Dyn 231:518–526Google Scholar
  28. Kobayashi T, Kajiura-Kobayashi H, Guan G, Nagahama Y (2008) Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus). Dev Dyn 237:297–306Google Scholar
  29. Lebrun C, Billard R, Jalabert B (1982) Changes in the number of germ cells in the gonads of the rainbow trout (Salmo gairdneri) during the first 10 post-hatching weeks. Reprod Nutr Dev 22:405–412Google Scholar
  30. Lewis ZR, McClellan MC, Postlethwait J, Cresko WA, Kaplan RH (2008) Female-specific increase in primordial germ cells marks sex differentiation in threespine stickleback (Gasterosteus aculeatus). J Morphol 269:909–921Google Scholar
  31. Marchand O, Govoroun M, D’Cotta H, McMeel O, Lareyre J-J, Bernot A, Laudet V, Guiguen Y (2000) DMRT1 expression during gonadal differentiation and spermatogenesis in the rainbow trout, Oncorhynchus mykiss. Biochim Biophys Acta 1493:180–187Google Scholar
  32. Masuyama H, Yamada M, Kamei Y, Fujiwara-Ishikawa T, Todo T, Nagahama Y, Matsuda M (2012) Dmrt1 mutation causes a male-to-female sex reversal after the sex determination by Dmy in the medaka. Chromosom Res 20:163–176CrossRefGoogle Scholar
  33. Matsuda M, Nagahama Y, Shinomiya A, Sato T, Matsuda C, Kobayashi T, Morrey CE, Shibata N, Asakawa S, Shimizu N, Hori H, Hamaguchi S, Sakaizumi M (2002) DMY is a Y-specific DM-domain gene required for male development in the medaka fish. Nature 417:559–563CrossRefPubMedGoogle Scholar
  34. Matsuda M, Shinomiya A, Kinoshita M, Suzuki A, Kobayashi T, Paul-Prasanth B, Lau EL, Hamaguchi S, Sakaizumi M, Nagahama Y (2007) DMY gene induces male development in genetically female (XX) medaka fish. PNAS 104:3865–3870Google Scholar
  35. Murozumi N, Nakashima R, Hirai T, Kamei Y, Ishikawa-Fujiwara T, Todo T, Kitano T (2014) Loss of follicle-stimulating hormone receptor function causes masculinization and suppression of ovarian development in genetically female medaka. Endocrinology 155:3136–3145CrossRefPubMedGoogle Scholar
  36. Nakamoto M, Matsuda M, Wang DS, Nagahama Y, Shibata N (2006) Molecular cloning and analysis of gonadal expression of Foxl2 in the medaka, Oryzias latipes. Biochem Biophys Res Commun 344:353–361Google Scholar
  37. Nakamura M, Kobayashi T, Chang XT, Nagahama Y (1998) Gonadal sex differentiation in teleost fish. J Exp Zool 281:362–372CrossRefGoogle Scholar
  38. Nozu R, Nakamura M (2015) Cortisol administration induces sex change from ovary to testis in the protogynous wrasse, Halichoeres trimaculatus. Sex Dev 9:118–124Google Scholar
  39. Patiño R, Davis KB, Schoore JE, Uguz C, Strüssmann CA, Parker NC, Simco BA, Goudie CA (1996) Sex differentiation of channel catfish gonads: normal development and effects of temperature. J Exp Zool 276:209–218CrossRefGoogle Scholar
  40. Paul-Prasanth B, Matsuda M, Lau EL, Suzuki A, Sakai F, Kobayashi T, Nagahama Y (2006) Knock-down of DMY initiates female pathway in the genetic male medaka, Oryzias latipes. Biochem Biophys Res Commun 351:815–819Google Scholar
  41. Piferrer F, Zanuy S, Carrillo M, Solar II, Devlin RH, Donaldson EM (1994) Brief treatment with an aromatase inhibitor during sex differentiation causes chromosomally female salmon to develop as normal, functional males. J Exp Zool 270:255–262CrossRefGoogle Scholar
  42. Robertson JG (1953) Sex differentiation in the Pacific salmon Oncorhynchus keta (Walbaum). Can J Zool 31:73–79Google Scholar
  43. Romer U, Beisensherz W (1996) Environmental determination of sex in Apistogramma (Cichlidae) and two other fresh water fishes (Teleostei). J Fish Biol 48:714–725Google Scholar
  44. Sato T, Endo T, Yamahira K, Hamaguchi S, Sakaizumi M (2005) Induction of female-to-male sex reversal by high temperature treatment in medaka, Oryzias latipes. Zool Sci 22:985–988Google Scholar
  45. Sato T, Suzuki A, Shibata N, Sakaizumi M, Hamaguchi S (2008) The novel mutant scl of the medaka fish, Oryzias latipes, shows no secondary sex characters. Zool Sci 25:299–306Google Scholar
  46. Satoh N, Egami N (1972) Sex differentiation of germ cells in the teleost, Oryzias latipes, during normal embryonic development. J Embryol Exp Morphol 28:385–395Google Scholar
  47. Shibata Y, Paul-Prasanth B, Suzuki A, Usami T, Nakamoto M, Matsuda M, Nagahama Y (2010) Expression of gonadal soma derived factor (GSDF) is spatially and temporally correlated with early testicular differentiation in medaka. Gene Expr Patterns 10:283–289CrossRefPubMedGoogle Scholar
  48. Shimizu M, Takahashi H (1980) Process of sex differentiation of the gonad and gonoduct of the three-spined stickleback, Gasterosteus aculeatus L. Bull Fac Fish Hokkaido Univ 31:137–148Google Scholar
  49. Strüssmann CA, Moriyama S, Hanke EF, Cota JCC, Takashima F (1996) Evidence of thermolabile sex determination in pejerrey. J Fish Biol 48:643–651Google Scholar
  50. Strüssmann CA, Saito T, Usui M, Yamada H, Takashima F (1997) Thermal thresholds and critical period of thermolabile sex determination in two atherinid fishes, Odontesthes bonariensis and Patagonina hatcheri. J Exp Zool 278:167–177Google Scholar
  51. Suzuki A, Tanaka M, Shibata N (2004) Expression of aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes. J Exp Zool 301:266–273Google Scholar
  52. Tabata K (1991) Induction of gynogenetic diploid males and presumption of sex determination mechanisms in the hirame Paralichthys olivaceus. Bull Jap Soc Sci Fish 57:845–850Google Scholar
  53. Vallowe HH (1957) Sexual differentiation in the teleost fish, Xiphophorus hellerii, as modified by experimental treatment. Biol Bull 112:422–429Google Scholar
  54. Wang D, Kobayashi T, Zhou L, Paul-Prasanth B, Ijiri S, Sakai F, Okubo K, Morohashi K, Nagahama Y (2007) Foxl2 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting with Ad4 binding protein/steroidogenic factor 1. Mol Endocrinol 21:712–725CrossRefPubMedGoogle Scholar
  55. Wendelaar Bonga SE (1997) The stress response in fish. Physiol Rev 77:591–625CrossRefPubMedGoogle Scholar
  56. Wolf LE (1931) History of the germ cells in the viviparous teleost Platypoecilus maculatus. J Morphol 52:428–439Google Scholar
  57. Yamaguchi T, Yamaguchi S, Hirai T, Kitano T (2007) Follicle-stimulating hormone signaling and Foxl2 are involved in transcriptional regulation of aromatase gene during gonadal sex differentiation in Japanese flounder, Paralichthys olivaseus. Biochem Biophys Res Commun 359:935–940Google Scholar
  58. Yamaguchi T, Yoshinaga N, Yazawa T, Gen K, Kitano T (2010) Cortisol is involved in temperature-dependent sex determination in the Japanese flounder. Endocrinology 151:3900–3908CrossRefPubMedGoogle Scholar
  59. Yamamoto T (1969) Sex differentiation. In: Hoar WS, Randall DJ (eds) Fish physiology, vol 3. Academic, New York, pp 117–175Google Scholar
  60. Yamamoto E (1995) Studies on sex-manipulation and production of cloned populations in hirame flounder, Paralichthys olivaceus (Temminek et Schlegel). Bull Tottori Pref Fish Exp Stn 34:1–145Google Scholar
  61. Yan H, Ijiri S, Wu Q, Kobayashi T, Li S, Nakaseko T, Adachi S, Nagahama Y (2012) Expression patterns of gonadotropin hormones and their receptors during early sexual differentiation in Nile tilapia Oreochromis niloticus. Biol Reprod 87(116):1–11Google Scholar
  62. Yoshinaga N, Shiraishi E, Yamamoto T, Iguchi T, Abe S, Kitano T (2004) Sexually dimorphic expression of a teleost homologue of Müllerian inhibiting substance during gonadal sex differentiation in Japanese flounder, Paralichthys olivaceus. Biochem Biophys Res Commun 322:508–513Google Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biological SciencesGraduate School of Science and Technology, Kumamoto UniversityChuo-kuJapan

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