Loss of the Proapoptotic BH3-Only Protein BCL-2 Modifying Factor Prolongs the Fertile Life Span in Female Mice1
Loss of the Proapoptotic BH3-Only Protein BCL-2 Modifying Factor Prolongs the Fertile Life Span in Female Mice1
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DOI：
10.1095/biolreprod.113.116947
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发表时间：
2014-04-01
影响因子：
3.6
通讯作者：
Hutt, Karla J.
中科院分区：
文献类型：
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作者：
Liew, Seng H.;Vaithiyanathan, Kavitha;Hutt, Karla J.
作为原始卵泡储存在卵巢中的卵母细胞的数量影响着女性可育寿命的持续时间。在胚胎和出生后的卵巢发育过程中，细胞死亡在决定卵巢内建立和维持多少原始卵泡方面起着关键作用。然而，单独的细胞凋亡调节因子在卵巢内介导细胞死亡的作用尚未被表征。在这项研究中，我们利用基因靶向的小鼠来研究bcl2家族中只有BH3亚群的促凋亡蛋白bcl2修饰因子(Bmf)在决定成体卵巢中维持的原始卵泡数量和生育寿命中的作用。卵巢体视学分析表明，出生后100、200、300和400天，BMF(-/-)小鼠的原始卵泡数量显著多于野生型(WT)对照组，但在第20天时差异不显著。在外源性促性腺激素刺激排卵后，野生型(WT)和野生型(WT)小鼠排出卵子的数量没有差异。Bmf(/)雌性具有繁殖力，每窝产仔数与WT雌性相同，但Bmf(-/-)雌性在6个月内比WT雌性更频繁地产仔，从而产生更多的后代。此外，BMF(-/-)雌虫的生育寿命比WT雌虫显著延长。我们的发现支持BMF在决定成体生殖生命中卵巢中维持的原始卵泡数量方面的重要作用，从而表明通过抑制BMF来增加卵巢中维持的原始卵泡数量可以延长女性的生育长度。
The duration of the female fertile life span is influenced by the number of oocytes stored in the ovary as primordial follicles. Cell death, both during ovarian development in the embryo and in the postnatal ovary, plays a critical role in determining how many primordial follicles are established and maintained within the ovary. However, the roles of individual apoptotic regulators in mediating cell death within the ovary have not yet been characterized. In this study, gene targeted mice were used to investigate the role of BCL-2-modifying factor (BMF), a proapoptotic protein belonging to the BH3-only subgroup of the BCL-2 family, in determining the number of primordial follicles maintained in the adult ovary and the length of the fertile life span. Stereological analysis of ovaries showed that Bmf (-/-) mice had significantly more primordial follicles than wild-type (WT) control animals at Postnatal Days 100, 200, 300, and 400 but not at Day 20. No differences were observed between WT and Bmf(-/-) mice in the number of ova shed following ovulatory stimulation with exogenous gonadotropins. Bmf (/) females were fertile and produced the same number pups/litter as WT females, but Bmf(-/-) females produced litters more frequently and consequently more offspring than WT females over a 6-mo period. Furthermore, the fertile life span of Bmf(-/-) females was significantly extended compared to WT females. Our findings support an important role for BMF in determining the number of primordial follicles maintained in the ovary throughout adult reproductive life and thus indicate that the length of female fertility may be extended by increasing the number of primordial follicles maintained within the ovary through inhibition of BMF.