Retinoic acid homeostasis through aldh1a2 and cyp26a1 mediates meiotic entry in Nile tilapia (Oreochromis niloticus).

Retinoic acid homeostasis through aldh1a2 and cyp26a1 mediates meiotic entry in Nile tilapia (Oreochromis niloticus).
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视黄酸稳态通过 aldh1a2 和 cyp26a1 介导尼罗罗非鱼 (Oreochromis niloticus) 的减数分裂进入

DOI:
10.1038/srep10131
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发表时间:
2015-05-15
期刊:
影响因子:
4.6
通讯作者:
Wang D
Wang D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Feng R;Fang L;Cheng Y;He X;Jiang W;Dong R;Shi H;Jiang D;Sun L;Wang D

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减数分裂是生殖细胞分化所特有的过程。视黄酸(RA)是控制四足动物减数分裂起始的性别特异性时间的关键因子,然而,RA在硬骨鱼类减数分裂起始中的作用尚不清楚。在这项研究中,基因编码的RA合酶aldh 1a 2,和分解代谢酶cyp 26 a1分离尼罗罗非鱼(Oreochromis niloticus),一种没有stra 8。在减数分裂开始前,卵巢和精巢中aldh 1a 2的表达上调,cyp 26 a1的表达下调。用RA合酶抑制剂处理或通过CRISPR/Cas9破坏Aldh 1a 2导致减数分裂起始延迟,同时下调cyp 26 a1和上调sycp 3。相比之下,治疗RA分解代谢酶的抑制剂和cyp 26 a1的破坏导致减数分裂的早期启动,与aldh 1a 2和sycp 3的表达增加。此外,用雌激素(E2)处理XY鱼和用法倔唑处理XX鱼导致性逆转和减数分裂起始逆转。这些结果表明,RA是必不可少的减数分裂起始在硬骨鱼通过stra 8独立的信号通路,其中aldh 1a 2和cyp 26 a1是至关重要的。与哺乳动物不同,E2是硬骨鱼类性别决定和减数分裂起始的主要调节因子。
Meiosis is a process unique to the differentiation of germ cells. Retinoic acid (RA) is the key factor controlling the sex-specific timing of meiotic initiation in tetrapods; however, the role of RA in meiotic initiation in teleosts has remained unclear. In this study, the genes encoding RA synthase aldh1a2, and catabolic enzyme cyp26a1 were isolated from Nile tilapia (Oreochromis niloticus), a species without stra8. The expression of aldh1a2 was up-regulated and expression of cyp26a1 was down-regulated before the meiotic initiation in ovaries and in testes. Treatment with RA synthase inhibitor or disruption of Aldh1a2 by CRISPR/Cas9 resulted in delayed meiotic initiation, with simultaneous down-regulation of cyp26a1 and up-regulation of sycp3. By contrast, treatment with an inhibitor of RA catabolic enzyme and disruption of cyp26a1 resulted in earlier meiotic initiation, with increased expression of aldh1a2 and sycp3. Additionally, treatment of XY fish with estrogen (E2) and XX fish with fadrozole led to sex reversal and reversion of meiotic initiation. These results indicate that RA is indispensable for meiotic initiation in teleosts via a stra8 independent signaling pathway where both aldh1a2 and cyp26a1 are critical. In contrast to mammals, E2 is a major regulator of sex determination and meiotic initiation in teleosts.
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