Abstract
BackgroundSex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens and aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing to characterise zebrafish gonadal transcriptomes and investigate the effects of 17α-methyltestosterone on gonadal differentiation.ResultsAt a morphological level, 17α-methyltestosterone (MT) masculinised gonads and accelerated spermatogenesis, and these changes were paralleled in masculinisation and de-feminisation of gonadal transcriptomes. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt1, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It also repressed expression of ovarian development and folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT treatment altered epigenetic modification of histones in zebrafish gonads. Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in control ovaries compared to MT-treated testes and control testes were not statistically significant during early gonad development (40 dpf).ConclusionOur study suggests that both androgen production and aromatase inhibition are important for androgen-induced gonadal masculinisation and natural testicular differentiation in zebrafish.
Highlights
Sex hormones play important roles in teleost ovarian and testicular development
Sex ratios and gonad histology of control zebrafish Sex ratios were determined via visualisation of enhanced green fluorescent protein (EGFP) fluorescence intensity of Tg(vas:egfp) zebrafish under a fluorescence microscope
In this study, we investigated the effects of MT treatment on zebrafish gonadal transcriptomes during gonadal differentiation
Summary
Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It repressed expression of ovarian development and folliculogenesis genes (bmp, gdf, figla, zp2.1 and zp3b). The major natural androgen in teleost fish is 11-ketotestosterone [4], which is converted from androstenedione and testosterone via the steroidogenic enzymes 11β-hydroxylase (Cyp11c1) and 11β-hydroxysteroid dehydrogenase (Hsd11b2) [10,11,12,13] The effects of these androgens are mediated by androgen receptors [10, 14]. Androgen induction of female-to-male sex reversal [15, 34] is routinely used for sex control in
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