Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium
Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium
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DOI：
10.1242/dev.170225
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发表时间：
2019-01-01
期刊：
影响因子：
4.6
通讯作者：
Mark, Manuel
中科院分区：
文献类型：
--
作者：
Teletin, Marius;Vernet, Nadege;Mark, Manuel
在哺乳动物中，全反式维甲酸(ATRA)有助于精子发生。它是由支持细胞(SC)和生殖细胞(GC)中存在的两种视黄醛脱氢酶(RALDH)合成的。为了确定ATRA的每个来源的相对贡献，我们产生了在生精上皮(SE)中缺乏所有RALDH活性的小鼠。我们发现，ATRA的SC来源和GC来源在青春期共同启动和传播精子发生波。在成年人中，它们发挥着多余的功能，与所有人的预期相反，GC来源的来源并没有发挥任何特定的作用，尽管它们贡献了睾丸中存在的ATRA总量的三分之二。SCs的产生足以维持SCs中基因的周期性表达，以及SE的周期和波动，这是导致精子稳定产生的原因。干细胞的产生也是受精所特别需要的。重要的是，我们的研究表明，精原细胞的分化依赖于在SE内由RALDH合成的ATRA，而精母细胞启动减数分裂和表达STRA8可以在没有ATRA的情况下发生。
In mammals, all-trans retinoic acid (ATRA) is instrumental to spermatogenesis. It is synthesized by two retinaldehyde dehydrogenases (RALDH) present in both Sertoli cells (SCs) and germ cells (GCs). In order to determine the relative contributions of each source of ATRA, we have generated mice lacking all RALDH activities in the seminiferous epithelium (SE). We show that both the SC- and GC-derived sources of ATRA cooperate to initiate and propagate spermatogenetic waves at puberty. In adults, they exert redundant functions and, against all expectations, the GC-derived source does not perform any specific roles despite contributing to two-thirds of the total amount of ATRA present in the testis. The production from SCs is sufficient to maintain the periodic expression of genes in SCs, as well and the cycle and wave of the SE, which account for the steady production of spermatozoa. The production from SCs is also specifically required for spermiation. Importantly, our study shows that spermatogonia differentiation depends upon the ATRA synthesized by RALDH inside the SE, whereas initiation of meiosis and expression of STRA8 by spermatocytes can occur without ATRA.