Spermatogonia Differentiation Requires Retinoic Acid Receptor γ
Spermatogonia Differentiation Requires Retinoic Acid Receptor γ
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DOI：
10.1210/en.2011-1102
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发表时间：
2012-01-01
期刊：
影响因子：
4.8
通讯作者：
Mark, Manuel
中科院分区：
文献类型：
--
作者：
Gely-Pernot, Aurore;Raverdeau, Mathilde;Mark, Manuel
维生素A对哺乳动物的生殖有帮助。其代谢物视黄酸（RA）通过结合并激活三种核受体同种型（RA受体（RAR）α（RARA）、RAR β和RAR γ（RARG）），以类维生素A的方式发挥作用。在这里，我们发现1）RARG由A排列（A（al））精原细胞表达，以及在A（al）到A（1）精原细胞的过渡期间，这是已知需要RA;和2）在整个小鼠中或特别是在精原细胞中消除Rarg，不影响减数分裂和精子发生，但在某些生精上皮细胞周期过程中损害A（al）向A（1）的转变。随着年龄的增长，这种现象产生的曲细精管只含有精原细胞和支持细胞。总之，我们的研究结果表明，RARG细胞自主转导，在未分化的精原细胞的成年睾丸，RA信号的精子发生的关键。然而，在青春期前生精波期间，RARG功能的丧失可以通过RARA来补偿，如在RARG缺失的睾丸中减数分裂细胞出现的正常时间所示。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Stra 8的表达。有趣的是，与维生素A缺乏相反，Rarg的失活不会损害精原细胞分化标志物Kit和Stra 8的表达。后一种观察结果支持了先前在支持细胞中工作的RA信号通路也参与精原细胞分化的观点。（内分泌学153：438-449，2012）
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)alpha (RARA), RAR beta, and RAR gamma (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. (Endocrinology 153: 438-449, 2012)