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. 2022 Sep 7;10:944776. doi: 10.3389/fcell.2022.944776

FIGURE 2.

FIGURE 2

Effects of manipulating estrogen signaling on the gonadal fate in fish, chickens, and mammals. (A) In fish: In female tilapia and zebrafish, both exposure to aromatase inhibitor fadrozole during sex determination and knockout of cyp19a1a cause primary ovary-to-testis sex reversal, while long-term fadrozole treatment of mature females leads to ovary-to-testis sex reversal. Therefore, cyp19a1a is involved in both primary ovarian differentiation and maintenance of ovarian identity. In medaka, exposure to fadrozole during sex determination has no effect on ovarian differentiation, while both cyp19a1a KO and treatment of adult females with aromatase inhibitor exemestane eventually masculinize the ovaries. This indicates that cyp19a1a is only involved in the maintenance of medaka ovarian identity. (B) In chickens: treatment with aromatase inhibitor fadrozole in ZW female embryos results in transient testis development. On the other hand, estradiol injection to ZZ male embryos results in ovary or ovotestis differentiation. Moreover, ovarian development is induced in male embryos overexpressing CYP19A1. (C,D) In mammals: (C) In marsupials. Effects of estradiol treatment on XY males varies from species to species. Newborn XY Virginia opossum exposed to estradiol for 30 days post-partum (dpp) develops ovaries or ovotestes, whereas newborn XY gray short-tailed opossum exposed for 9 dpp develops dysgenetic testes. Newborn XY wallaby exposed for 50 dpp develops ovaries or gonadal agenesis if born prematurely. (D) In placental mammals: In the mouse, Cyp19a1 knockout or Esr1/Esr2 double knockout leads to postnatal transdifferentiation of granulosa cells into Sertoli-like cells. This indicates a role in the maintenance of ovarian identity rather than in primary ovarian differentiation. In the rabbit, CYP19A1 knockout does not impair primary ovarian differentiation but prevents the proper development of ovaries, resulting in small ovaries and infertility. In humans, mutations in CYP19A1 or ESR1 or ESR2 genes do not impact primary ovarian differentiation but cause either streak ovaries or polycystic ovaries.