Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males
Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males
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DOI：
10.1073/pnas.1214883110
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发表时间：
2013-01-08
影响因子：
11.1
通讯作者：
Griswold, Michael D.
中科院分区：
文献类型：
--
作者：
Tong, Ming-Han;Yang, Qi-En;Griswold, Michael D.
视黄酸（RA）是一种活性维生素A衍生物，在哺乳动物精子发生过程中起重要作用.遗传学研究表明，维生素A通过视黄醇脱氢酶10（RDH10）氧化为视黄醇对胚胎RA生物合成至关重要。然而，Rdh10在出生后RA合成中的生理作用仍不清楚，因为Rdh10功能丧失突变导致早期胚胎死亡。我们在出生后小鼠睾丸中进行了Rdh10的体内遗传研究，发现Rdh10在支持细胞中缺乏，但在生殖细胞中没有，导致轻度生殖细胞耗竭表型。青少年小鼠的支持细胞和生殖细胞中RDH10的缺乏导致精原细胞分化的阻断，类似于维生素A缺乏动物中所见。这种精子发生缺陷是由于幼年睾丸RA合成完全缺乏引起的，可以通过给予维甲酸来挽救。因此，在幼年小鼠中，睾丸中RA的主要但非唯一来源是支持细胞。相反，成年Rdh10缺陷小鼠表现出正常的精子发生表型，表明在发展过程中发生的变化，无论是在RA的细胞来源或参与RA合成的视黄醇脱氢酶。
Retinoic acid (RA), an active vitamin A derivative, is essential for mammalian spermatogenesis. Genetic studies have revealed that oxidation of vitamin A to retinal by retinol dehydrogenase 10 (RDH10) is critical for embryonic RA biosynthesis. However, physiological roles of RDH10 in postnatal RA synthesis remain unclear, given that Rdh10 loss-of-function mutations lead to early embryonic lethality. We conducted in vivo genetic studies of Rdh10 in postnatal mouse testes and found that an RDH10 deficiency in Sertoli cells, but not in germ cells, results in a mild germ cell depletion phenotype. A deficiency of RDH10 in both Sertoli and germ cells in juvenile mice results in a blockage of spermatogonial differentiation, similar to that seen in vitamin A-deficient animals. This defect in spermatogenesis arises from a complete deficiency in juvenile testicular RA synthesis and can be rescued by retinoid administration. Thus, in juvenile mice, the primary, but not exclusive, source of RA in the testes is Sertoli cells. In contrast, adult Rdh10-deficient mice exhibit phenotypically normal spermatogenesis, indicating that during development a change occurs in either the cellular source of RA or the retinaldehyde dehydrogenase involved in RA synthesis.