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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >PNAS Plus: Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis
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PNAS Plus: Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis

机译：PNAS Plus：减数分裂和体细胞定期产生维甲酸可协调小鼠精子发生的四个转变

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Mammalian spermatogenesis is an elaborately organized differentiation process, starting with diploid spermatogonia, which include germ-line stem cells, and ending with haploid spermatozoa. The process involves four pivotal transitions occurring in physical proximity: spermatogonial differentiation, meiotic initiation, initiation of spermatid elongation, and release of spermatozoa. We report how the four transitions are coordinated in mice. Two premeiotic transitions, spermatogonial differentiation and meiotic initiation, were known to be coregulated by an extrinsic signal, retinoic acid (RA). Our chemical manipulations of RA levels in mouse testes now reveal that RA also regulates the two postmeiotic transitions: initiation of spermatid elongation and spermatozoa release. We measured RA concentrations and found that they changed periodically, as also reflected in the expression patterns of an RA-responsive gene, STRA8; RA levels were low before the four transitions, increased when the transitions occurred, and remained elevated thereafter. We found that pachytene spermatocytes, which express an RA-synthesizing enzyme, Aldh1a2, contribute directly and significantly to RA production in testes. Indeed, chemical and genetic depletion of pachytene spermatocytes revealed that RA from pachytene spermatocytes was required for the two postmeiotic transitions, but not for the two premeiotic transitions. We conclude that the premeiotic transitions are coordinated by RA from Sertoli (somatic) cells. Once germ cells enter meiosis, pachytene spermatocytes produce RA to coordinate the two postmeiotic transitions. In combination, these elements underpin the spatiotemporal coordination of spermatogenesis and ensure its prodigious output in adult males.
机译：哺乳动物的精子发生是一个精心组织的分化过程，始于二倍体精原细胞，其中包括种系干细胞，最后是单倍体精子。该过程涉及在物理上邻近发生的四个关键转变：精原细胞分化，减数分裂起始，精子伸长起始和精子释放。我们报告四个过渡如何在小鼠中协调。已知两个减数分裂前的过渡，精原细胞分化和减数分裂的起始，是由外在信号视黄酸（RA）调控的。现在，我们在小鼠睾丸中对RA水平进行化学处理后发现，RA还可以调节两个减数分裂后的过渡：精子伸长的启动和精子的释放。我们测量了RA的浓度，发现它们定期变化，这也反映在RA反应基因STRA8的表达模式中。四个过渡之前的RA水平较低，过渡出现时RA水平升高，此后仍保持较高水平。我们发现，表达RA合成酶Aldh1a2的粗精子细胞直接和显着地促进了睾丸中RA的产生。确实，粗线精细胞的化学和遗传耗竭表明，从粗线精细胞的RA是两个减数分裂后过渡所必需的，而不是两个减数分裂前过渡所必需的。我们得出结论，减数分裂前的过渡是由Sertoli（体细胞）的RA协调的。一旦生殖细胞进入减数分裂，粗线精原细胞产生RA来协调两个减数分裂后的过渡。这些元素结合在一起，可以支撑精子发生的时空协调，并确保其在成年男性中的大量输出。

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