Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary

Abstract

Induction of sex reversal of XY fish has been restricted to the sex undifferentiated period. In the present study, differentiated XY tilapia were treated with trilostane (TR), metopirone (MN) and glycyrrhetinic acid (GA) (inhibitor of 3β-HSD, Cyp11b2 and 11β-HSD, respectively) alone or in combination with 17β-estradiol (E2) from 30 to 90 dah (days after hatching). At 180 dah, E2 alone resulted in 8.3%, and TR, MN and GA alone resulted in no secondary sex reversal (SSR), whereas TR + E2, MN + E2 and GA + E2 resulted in 88.3, 60.0 and 46.7% of SSR, respectively. This sex reversal could be rescued by simultaneous administration of 11-ketotestosterone (11-KT). Compared with the control XY fish, decreased serum 11-KT and increased E2 level were detected in SSR fish. Immunohistochemistry analyses revealed that Cyp19a1a, Cyp11b2 and Dmrt1 were expressed in the gonads of GA + E2, MN + E2 and TR + E2 SSR XY fish at 90 dah, but only Cyp19a1a was expressed at 180 dah. When the treatment was applied from 60 to 120 dah, TR + E2 resulted in 3.3% of SSR, MN + E2 and GA + E2 resulted in no SSR. These results demonstrated that once 11-KT was synthesized, it could antagonize E2-induced male-to-female SSR, which could be abolished by simultaneous treatment with the inhibitor of steroidogenic enzymes. The upper the enzyme was located in the steroidogenic pathway, the higher SSR rate was achieved when it was inhibited as some of the precursors, such as androstenedione, testosterone and 5α-dihydrotestosterone, could act as androgens. These results highlight the key role of androgen in male sex maintenance.

Anti-masculinization induced by aromatase inhibitors in adult female zebrafish

“…The downregulation of endogenous estrogen induces female trans-differentiation in juvenile and adult fish [17,28]. Impairing androgen synthesis and elevating exogenous estrogen can induce the male trans-differentiation in adult tilapia while exogenous estrogen alone can direct sex differentiation to female in juvenile fish [29]. These observations indicate the effects of sex hormone in the sex differentiation and maintenance in fish [30].…”

Hsd3b2 associated in modulating steroid hormone synthesis pathway regulates the differentiation of chicken embryonic stem cells into spermatogonial stem cells

“…In mammals, the addition of estrogen could reverse the testis to the ovaries when blocking the expression of androgen. 21 Moreover, testosterone, as a hormone maintaining the male gonadal function, could improve the differentiation efficiency of insulin-producing cells from human induced pluripotent stem cells, regulate the adipose cell differentiation and promote proliferation and differentiation of rat myoblasts. [22][23][24] Additionally, the normal concentration of testosterone in human ranges from 14 to 25.4 nmol/L and different concentrations (10 −13 ∼ 10 −5 mol/L) of testosterone could induce 3T3-L1pre-adipocyte differentiation.…”

“…Recently studies have revealed that sex hormones which could maintain gender and sexuality may accelerate the cell differentiation. In mammals, the addition of estrogen could reverse the testis to the ovaries when blocking the expression of androgen . Moreover, testosterone, as a hormone maintaining the male gonadal function, could improve the differentiation efficiency of insulin‐producing cells from human induced pluripotent stem cells, regulate the adipose cell differentiation and promote proliferation and differentiation of rat myoblasts .…”

Involvement of IGF-1R-PI3K-AKT-mTOR pathway in increased number of GnRH3 neurons during androgen-induced sex reversal of the brain in female tilapia

“…Since male tilapia grow approximately twice as fast as females, a monosex population of sex-reversed males is commercially produced using androgen-supplemented feed. The mechanisms underlying sex differentiation and hormone-induced sex reversal of the gonads during early development have been well studied in tilapia 8 – 13 . However, the mechanisms underlying sex reversal in the tilapia brain remain unsolved.…”