Molecular Mechanisms of Sexual Plasticity in Fishes
LiNa Sun1,2, MingHui Li1,2, DeShou Wang*1,2
1. Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University, Chongqing, 400715, China.
2. School of Life Sciences, Southwest University, Chongqing, 400715, China.
In fish, sex is determined either genetically (genetic sex determination, GSD) or environmentally (environmental sex determination, ESD), or a combination of both. Natural sex reversal (NSR) occurs in more than 300 species (hermaphrodites, either protandrous or protogynous). In gonochorists, Primary sex reversal (PSR) could be induced by hormone or thermal treatment. Secondary sex reversal (SSR) could be induced even after sex differentiation or at adult stage. Recently, sex reversal could also be achieved by transgene or gene knockout (Transgenic sex reversal, TSR). These results indicated that fish sex is quite plastic. Tilapia is a good for investigation of the molecular mechanisms for sexual plasticity. In tilapia, complete sex reversal could be achieved by transgene or knockout of not only master sex determining genes (SDG), but also key genes in female and male pathway. Interestingly, knockout of these genes also resulted in turnover of the SDG, sex chromosome, or even sex determination system. Administration of aromatase inhibitor in XX fish was able to induce primary sex reversal when applied before sex differentiation and secondary sex reversal when applied after sex differentiation. Simultaneous treatment with estrogen and androgen before sexual differentiation resulted in all females in both XX and XY fish. On the other hand, administration of exogenous estrogen alone can reverse XY fish to phenotypic females when applied during the narrow window of sex differentiation. Blockage of androgen synthesis and simultaneous administration of estrogen in XY fish can even induce the transdifferentiation of differentiated testis into functional ovary. Homozygous mutation of foxl2 and cyp19a1a in XX fish by CRISPR/Cas9 resulted in female to male sex reversal which could be rescued by exogenous estrogen treatment; while knockout of amhy, amhr2 and gsdf in XY fish resulted in male to female sex reversal which could be rescued by exogenous androgen treatment. Taken together, these results strongly emphasize the sexual plasticity of fish, the critical roles of endogenous estrogen in female sex differentiation and maintenance and endogenous androgen in male sex maintenance. The molecular mechanism for sexual plasticity in fish lies in the sensitivity of the key genes in the male and female pathway to the endogenous and exogenous cues.
Key Words: Tilapia; Sexual plasticity; Molecular mechanism; Sex determination and differentiation
LiNa Sun1,2, MingHui Li1,2, DeShou Wang*1,2
1. Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University, Chongqing, 400715, China.
2. School of Life Sciences, Southwest University, Chongqing, 400715, China.
In fish, sex is determined either genetically (genetic sex determination, GSD) or environmentally (environmental sex determination, ESD), or a combination of both. Natural sex reversal (NSR) occurs in more than 300 species (hermaphrodites, either protandrous or protogynous). In gonochorists, Primary sex reversal (PSR) could be induced by hormone or thermal treatment. Secondary sex reversal (SSR) could be induced even after sex differentiation or at adult stage. Recently, sex reversal could also be achieved by transgene or gene knockout (Transgenic sex reversal, TSR). These results indicated that fish sex is quite plastic. Tilapia is a good for investigation of the molecular mechanisms for sexual plasticity. In tilapia, complete sex reversal could be achieved by transgene or knockout of not only master sex determining genes (SDG), but also key genes in female and male pathway. Interestingly, knockout of these genes also resulted in turnover of the SDG, sex chromosome, or even sex determination system. Administration of aromatase inhibitor in XX fish was able to induce primary sex reversal when applied before sex differentiation and secondary sex reversal when applied after sex differentiation. Simultaneous treatment with estrogen and androgen before sexual differentiation resulted in all females in both XX and XY fish. On the other hand, administration of exogenous estrogen alone can reverse XY fish to phenotypic females when applied during the narrow window of sex differentiation. Blockage of androgen synthesis and simultaneous administration of estrogen in XY fish can even induce the transdifferentiation of differentiated testis into functional ovary. Homozygous mutation of foxl2 and cyp19a1a in XX fish by CRISPR/Cas9 resulted in female to male sex reversal which could be rescued by exogenous estrogen treatment; while knockout of amhy, amhr2 and gsdf in XY fish resulted in male to female sex reversal which could be rescued by exogenous androgen treatment. Taken together, these results strongly emphasize the sexual plasticity of fish, the critical roles of endogenous estrogen in female sex differentiation and maintenance and endogenous androgen in male sex maintenance. The molecular mechanism for sexual plasticity in fish lies in the sensitivity of the key genes in the male and female pathway to the endogenous and exogenous cues.
Key Words: Tilapia; Sexual plasticity; Molecular mechanism; Sex determination and differentiation