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解析雌雄生殖细胞减数分裂调控中的分子事件。

Resolving molecular events in the regulation of meiosis in male and female germ cells.

机构信息

Sanford-Burnham Medical Research Institute, Development and Aging Program, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Sci Signal. 2013 Aug 13;6(288):pe25. doi: 10.1126/scisignal.2004530.

Abstract

In mammalian species, the process of meiosis, in which genes are randomly assorted between parental chromosomes during formation of egg and sperm cells, occurs prenatally in females but postnatally in males. To understand sex-specific differences in signaling mechanisms that underlie fertility, many studies have focused on identifying factors that control meiotic induction. Studies in mice using genetic knockout of the transcriptional regulator Polycomb repressive complex-1 (PRC1) and pharmacological inhibition of retinoic acid (RA) signaling suggest that PRC1 prevents female meiotic induction until release of PRC1 repression by increased RA signaling in the ovary. However, genetic studies with mice lacking RA synthesis in reproductive tissues indicate that RA is required for male but not female meiosis, suggesting that RA functions as a male-specific inducer of meiosis and that another factor releases PRC1 repression to initiate female meiosis. Correct resolution of the molecular events governing female and male meiosis is important for treating infertility and devising improved birth control strategies.

摘要

在哺乳动物物种中,减数分裂过程中,基因在卵子和精子细胞形成过程中随机分配到亲本染色体上,在雌性中发生在产前,而在雄性中发生在产后。为了了解生殖信号机制中的性别特异性差异,许多研究都集中在鉴定控制减数分裂诱导的因素上。使用转录调节因子多梳抑制复合物 1 (PRC1) 的基因敲除和视黄酸 (RA) 信号的药理学抑制的小鼠研究表明,PRC1 阻止雌性减数分裂诱导,直到卵巢中 RA 信号增加释放 PRC1 抑制。然而,生殖组织中缺乏 RA 合成的小鼠遗传研究表明,RA 是雄性减数分裂所必需的,但不是雌性减数分裂所必需的,这表明 RA 作为一种雄性特异性减数分裂诱导因子发挥作用,而另一种因子释放 PRC1 抑制以启动雌性减数分裂。正确解决控制雌性和雄性减数分裂的分子事件对于治疗不孕和设计改进的避孕策略非常重要。

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