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首页> 外文期刊>Endocrinology >Transdifferentiation of differentiated ovary into functional testis by long-term treatment of aromatase inhibitor in Nile tilapia
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Transdifferentiation of differentiated ovary into functional testis by long-term treatment of aromatase inhibitor in Nile tilapia

机译：长期治疗尼罗罗非鱼的芳香化酶抑制剂可将分化的卵巢转分化为功能性睾丸

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摘要

Females with differentiated ovary of a gonochoristic fish, Nile tilapia, were masculinized by long-term treatment with an aromatase inhibitor (Fadrozole) in the present study. The reversed gonads developed into functional testes with fertile sperm. The longer the fish experienced sex differentiation, the longer treatment time was needed for successful sex reversal. Furthermore, Fadrozole-induced sex reversal, designated as secondary sex reversal (SSR), was successfully rescued by supplement of exogenous 17β-estradiol. Gonadal histology, immunohistochemistry, transcriptome, and serum steroid level were analyzed during SSR. The results indicated that spermatogonia were transformed from oogonia or germline stem cell-like cells distributed in germinal epithelium, whereas Leydig and Sertoli cells probably came from the interstitial cells and granulosa cells of the ovarian tissue, respectively. The transdifferentiation of somatic cells, as indicated by the appearance of doublesex- and Mab-3-related transcription factor 1 (pre-Sertoli cells) and cytochrome P450, family 11, subfamily B, polypeptide 2 (pre-Leydig cells)-positive cells in the ovary, provided microniche for the transdifferentiation of germ cells. Decrease of serum 17β-estradiol was detected earlier than increase of serum 11-ketotestosterone, indicating that decrease of estrogen was the cause, where as increase of androgen was the consequence of SSR. The sex-reversed gonad displayed more similarity in morphology and histology with a testis, whereas the global gene expression profiles remained closer to the female control. Detailed analysis indicated that transdifferentiation was driven by suppression of female pathway genes and activation of male pathway genes. In short, SSR provides a good model for study of sex reversal in teleosts and for understanding of sex determination and differentiation in nonmammalian vertebrates.
机译：在本研究中，通过长期使用芳香化酶抑制剂（Fadrozole）治疗，男性化了具有生殖器生殖腺的鱼，即尼罗罗非鱼。倒性腺发育成具有可育精子的功能性睾丸。鱼经历性别分化的时间越长，成功进行性别逆转需要的治疗时间就越长。此外，通过补充外源性17β-雌二醇成功地挽救了Fadrozole诱导的性逆转，称为二次性逆转（SSR）。在SSR期间分析了性腺组织学，免疫组织化学，转录组和血清类固醇水平。结果表明，精原细胞是由分布在生发上皮中的卵原细胞或种系干细胞样细胞转化而来的，而精巢细胞和支持细胞可能分别来自卵巢组织的间质细胞和颗粒细胞。体细胞的转分化，如双性相关和与Mab-3相关的转录因子1（塞托利前细胞）和细胞色素P450，家族11，亚家族B，多肽2（Leydig前细胞）阳性细胞的出现所表明在卵巢中，为生殖细胞的转分化提供了微生态位。血清17β-雌二醇降低的时间要早​​于血清11-酮睾酮的升高，这表明雌激素的降低是原因，而雄激素的升高是SSR的结果。性逆转的性腺在形态和组织学上显示出与睾丸的更多相似性，而总体基因表达谱仍然更接近女性对照。详细的分析表明，转分化是由抑制女性途径基因和激活男性途径基因驱动的。简而言之，SSR为研究硬骨鱼的性逆转以及了解非哺乳动物脊椎动物的性别决定和分化提供了一个很好的模型。

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