ALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries.
ALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries.
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DOI：
10.1038/ncomms10845
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发表时间：
2016-02-19
影响因子：
16.6
通讯作者：
Koopman P
中科院分区：
文献类型：
--
作者：
Bowles J;Feng CW;Miles K;Ineson J;Spiller C;Koopman P
大量证据表明，在哺乳动物的胎儿卵巢发育过程中，视黄酸（RA）诱导生殖细胞表达减数分裂前标志物Stra8并进入减数分裂，而这些作用在胎儿睾丸中被RA降解P450酶CYP 26 B1阻止。尽管如此，RA的作用一直存在争议，主要是因为胚胎中的生殖细胞缺乏两种主要的RA合成酶ALDH1A2和ALDH1A3，仍然能够进入减数分裂。在这里，我们表明，第三RA合成酶，ALDH1A1，在胎儿卵巢中表达，提供了一个可能的来源RA在ALDH1A2和ALDH1A3的情况下。在缺乏ALDH1A1的卵巢中，生殖细胞减数分裂的开始被延迟。我们的数据解决了由相互矛盾的已发表数据集所引起的难题，并再次证实了减数分裂是由发育中的卵巢中的内源性RA触发的模型。 最近的研究结果挑战了已建立的概念，视黄酸（RA）诱导胎儿生殖细胞进入减数分裂。Bowles等鉴定出ALDH1A1酶是卵巢RA的来源，即使在其他RA合成酶缺失的情况下，也可能诱导减数分裂。
Substantial evidence exists that during fetal ovarian development in mammals, retinoic acid (RA) induces germ cells to express the pre-meiotic marker Stra8 and enter meiosis, and that these effects are prevented in the fetal testis by the RA-degrading P450 enzyme CYP26B1. Nonetheless, the role of RA has been disputed principally because germ cells in embryos lacking two major RA-synthesizing enzymes, ALDH1A2 and ALDH1A3, remain able to enter meiosis. Here we show that a third RA-synthesizing enzyme, ALDH1A1, is expressed in fetal ovaries, providing a likely source of RA in the absence of ALDH1A2 and ALDH1A3. In ovaries lacking ALDH1A1, the onset of germ cell meiosis is delayed. Our data resolve the conundrum posed by conflicting published data sets and reconfirm the model that meiosis is triggered by endogenous RA in the developing ovary. Recent findings have challenged the established concept that retinoic acid (RA) induces foetal germ cells to enter meiosis. Here, Bowles et al. identify the enzyme ALDH1A1 as a source of ovarian RA that may induce meiosis even when other RA-synthetic enzymes are deleted.