Retinoic Acid Induces Multiple Hallmarks of the Prospermatogonia-to-Spermatogonia Transition in the Neonatal Mouse
Retinoic Acid Induces Multiple Hallmarks of the Prospermatogonia-to-Spermatogonia Transition in the Neonatal Mouse
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DOI：
10.1095/biolreprod.113.114645
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发表时间：
2014-03-01
影响因子：
3.6
通讯作者：
Geyer, Christopher B.
中科院分区：
文献类型：
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作者：
Busada, Jonathan T.;Kaye, Evelyn P.;Geyer, Christopher B.
在哺乳动物中，大多数新生雄性生殖细胞（原生殖细胞）是静止的，位于睾丸索的中心。在对未知信号的反应中，精原细胞转变为精原细胞，重新进入细胞周期，分裂并移动到睾丸索的周围。在小鼠中，这些事件在产后3-4天（dpp）发生，这在时间上与新生儿睾丸中的视黄酸（RA）信号传导的开始一致。RA在启动两性生殖细胞进入减数分裂中具有关键作用，但对RA信号传导的机制和下游细胞变化知之甚少。我们研究了RA在体内介导精原细胞向精原细胞过渡的作用，发现早熟RA诱导的生殖细胞变化在24小时内模仿了3-4 dpp内源性过渡期间发生的变化。这些变化包括：1）精原细胞增殖; 2）细胞器的成熟;和3）分化精原细胞特征性标志物的表达。我们发现，生殖细胞暴露于RA并没有导致细胞凋亡损失，而是导致延迟; 2天进入减数分裂。两者合计，我们的研究结果表明，外源性RA诱导的精原细胞进入减数分裂前的精原细胞的过渡的多个标志。
In mammals, most neonatal male germ cells (prospermatogonia) are quiescent and located in the center of the testis cords. In response to an unknown signal, prospermatogonia transition into spermatogonia, reenter the cell cycle, divide, and move to the periphery of the testis cords. In mice, these events occur by 3-4 days postpartum (dpp), which temporally coincides with the onset of retinoic acid (RA) signaling in the neonatal testis. RA has a pivotal role in initiating germ cell entry into meiosis in both sexes, yet little is known about the mechanisms and about cellular changes downstream of RA signaling. We examined the role of RA in mediating the prospermatogonia-to-spermatogonia transition in vivo and found 24 h of precocious RA exposure-induced germ cell changes mimicking those that occur during the endogenous transition at 3-4 dpp. These changes included: 1) spermatogonia proliferation; 2) maturation of cellular organelles; and 3), expression of markers characteristic of differentiating spermatogonia. We found that germ cell exposure to RA did not lead to cellular loss from apoptosis but rather resulted in a delay of; 2 days in their entry into meiosis. Taken together, our results indicate that exogenous RA induces multiple hallmarks of the transition of prospermatogonia to spermatogonia prior to their entry into meiosis.