Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de Santé et de Recherche Médicale Unité 964, Centre National de Recherche Scientifique Unité Mixte de Recherche 7104, Université de Strasbourg, 67404 Illkirch, France.
Endocrinology. 2012 Jan;153(1):438-49. doi: 10.1210/en.2011-1102. Epub 2011 Nov 1.
Vitamin A is instrumental to mammalian reproduction. Its metabolite, retinoic acid (RA), acts in a hormone-like manner through binding to and activating three nuclear receptor isotypes, RA receptor (RAR)α (RARA), RARβ, and RARγ (RARG). Here, we show that 1) RARG is expressed by A aligned (A(al)) spermatogonia, as well as during the transition from A(al) to A(1) spermatogonia, which is known to require RA; and 2) ablation of Rarg, either in the whole mouse or specifically in spermatogonia, does not affect meiosis and spermiogenesis but impairs the A(al) to A(1) transition in the course of some of the seminiferous epithelium cycles. Upon ageing, this phenomenon yields seminiferous tubules containing only spermatogonia and Sertoli cells. Altogether, our findings indicate that RARG cell-autonomously transduces, in undifferentiated spermatogonia of adult testes, a RA signal critical for spermatogenesis. During the prepubertal spermatogenic wave, the loss of RARG function can however be compensated by RARA, as indicated by the normal timing of appearance of meiotic cells in Rarg-null testes. Accordingly, RARG- and RARA-selective agonists are both able to stimulate Stra8 expression in wild-type prepubertal testes. Interestingly, inactivation of Rarg does not impair expression of the spermatogonia differentiation markers Kit and Stra8, contrary to vitamin A deficiency. This latter observation supports the notion that the RA-signaling pathway previously shown to operate in Sertoli cells also participates in spermatogonia differentiation.
维生素 A 对哺乳动物的繁殖至关重要。其代谢产物视黄酸（RA）通过与三种核受体亚型（RARα（RARA）、RARβ 和 RARγ（RARG））结合并激活它们，以类似激素的方式发挥作用。在这里，我们表明：1）RARG 在 A 型精原细胞（A(al)）以及从 A(al)到 A(1)精原细胞的过渡中表达，已知这一过程需要 RA；2）在整个小鼠或特异性地在精原细胞中敲除 Rarg，不会影响减数分裂和精子发生，但会在一些生精上皮周期中损害 A(al)到 A(1)的过渡。随着年龄的增长，这种现象导致仅含有精原细胞和支持细胞的曲细精管。总之，我们的研究结果表明，RARG 细胞自主地在成年睾丸的未分化精原细胞中传递 RA 信号，这对于精子发生至关重要。然而，在青春期前的精子发生波中，RARG 功能的丧失可以被 RARA 代偿，这表明在 Rarg 缺失的睾丸中，减数分裂细胞出现的时间正常。因此，RARG 和 RARA 选择性激动剂都能够刺激野生型青春期前睾丸中 Stra8 的表达。有趣的是，与维生素 A 缺乏相反，Rarg 的失活并不损害精原细胞分化标志物 Kit 和 Stra8 的表达。后一种观察结果支持了先前表明在支持细胞中起作用的 RA 信号通路也参与精原细胞分化的观点。
