Sex Determination and Differentiation in Teleost: Roles of Genetics, Environment, and Brain

Abstract

The fish reproductive system is a complex biological system. Nonetheless, reproductive organ development is conserved, which starts with sex determination and then sex differentiation. The sex of a teleost is determined and differentiated from bipotential primordium by genetics, environmental factors, or both. These two processes are species-specific. There are several prominent genes and environmental factors involved during sex determination and differentiation. At the cellular level, most of the sex-determining genes suppress the female pathway. For environmental factors, there are temperature, density, hypoxia, pH, and social interaction. Once the sexual fate is determined, sex differentiation takes over the gonadal developmental process. Environmental factors involve activation and suppression of various male and female pathways depending on the sexual fate. Alongside these factors, the role of the brain during sex determination and differentiation remains elusive. Nonetheless, GnRH III knockout has promoted a male sex-biased population, which shows brain involvement during sex determination. During sex differentiation, LH and FSH might not affect the gonadal differentiation, but are required for regulating sex differentiation. This review discusses the role of prominent genes, environmental factors, and the brain in sex determination and differentiation across a few teleost species.

Keywords: bipotential gonad; brain; sex determination; sex differentiation.

Figure 1

Basic pathway of gonadal development from bipotential gonadal primordium to become a testis or an ovary.

Figure 2

The schematic diagram of the uncertain pathway in the gonadal sex determination and sexual differentiation of the brain. (A) The role of the brain during sex determination remains elusive. There is only one study in zebrafish that shows that GnRH III knockout has resulted in a male sex-biased population. To date, there is no evidence showing LH and FSH directly regulate the expression of sex-determining genes (amhr2, amhy, dmrt1, dmy, gdf6Y, gsdf, and sdY). (B) The role of testosterone (T) and oestrogen involved in masculinisation and feminisation in a fish, respectively. Nonetheless, whether the gonads initially differentiated into testes or ovaries followed by sexual differentiation of the brain, or vice versa, is unknown.

Figure 3

Schematic representation of sex determination/differentiation in teleost. Undifferentiated germ cells need the surrounding somatic cells to provide an instructive signal(s) to initiate sexual differentiation. Therefore, the first step of oogenesis and spermatogenesis is managed by somatic cells [93]. From fish to mammals, Amh signalling plays an important role in gonadal development [13]. In Japanese medaka, gsdf null mutants and amhr2 mutants show excessive growth of germ cells and oocyte arrest during the previtellogenic stage [94]. In zebrafish, gsdf and amh are essential to inhibit the accumulation of premature oocytes [95]. This suggests the expression of gsdf and amh/amhr2 have to be stable during the sex differentiation phase of gonadal development. Reduced gsdf or amh through the amhr2 can directly or indirectly result in protandry [53,97,98]. Ovotestis development is the result of differentially expressed gsdf gene and in amhr2 mutants. Therefore, gsdf and amh signalling is vital for gametogenesis, the production of sex steroids and the secretion of gonadotropins [94].