Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation
Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation
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DOI：
10.1128/mcb.01919-06
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发表时间：
2007-03-01
影响因子：
5.3
通讯作者：
Conti, Marco
中科院分区：
文献类型：
--
作者：
Hsieh, Minnie;Lee, Daekee;Conti, Marco
在排卵前卵泡中，哺乳动物卵母细胞维持在减数分裂前期停滞状态，直到促黄体生成素（LH）峰诱导重新进入第一次减数分裂。卵母细胞周围的体细胞和卵泡壁的显著变化也由LH诱导，并且是排卵所必需的。在这里，我们提供的遗传证据表明，LH依赖性的表皮生长因子受体（EGFR）的反式激活是必不可少的卵母细胞重新进入减数分裂细胞周期，为合成的细胞外基质周围的卵母细胞，导致卵丘扩张，并在体内卵泡破裂。缺乏两种EGFR配体双调蛋白或表皮调节蛋白的小鼠显示卵母细胞成熟和卵丘扩张延迟或减少。在化合物突变小鼠中，其中一种EGFR配体的丢失与EGFR的亚纯型等位基因的信号传导减少相关，LH不再发出卵母细胞减数分裂恢复的信号。此外，在这些小鼠中，涉及卵丘扩张和卵泡破裂的基因的诱导受到损害，导致排卵受损。因此，这些研究表明，LH诱导的表皮生长因子样生长因子和EGFR反式激活是必不可少的一个关键的生理过程，如排卵的调节，并提供了新的策略，操纵生育。
In the preovulatory ovarian follicle, mammalian oocytes are maintained in prophase meiotic arrest until the luteinizing hormone (LH) surge induces reentry into the first meiotic division. Dramatic changes in the somatic cells surrounding the oocytes and in the follicular wall are also induced by LH and are necessary for ovulation. Here, we provide genetic evidence that LH-dependent transactivation of the epidermal growth factor receptor (EGFR) is indispensable for oocyte reentry into the meiotic cell cycle, for the synthesis of the extracellular matrix surrounding the oocyte that causes cumulus expansion, and for follicle rupture in vivo. Mice deficient in either amphiregulin or epiregulin, two EGFR ligands, display delayed or reduced oocyte maturation and cumulus expansion. In compound-mutant mice in which loss of one EGFR ligand is associated with decreased signaling from a hypomorphic allele of the EGFR, LH no longer signals oocyte meiotic resumption. Moreover, induction of genes involved in cumulus expansion and follicle rupture is compromised in these mice, resulting in impaired ovulation. Thus, these studies demonstrate that LH induction of epidermal growth factor-like growth factors and EGFR transactivation are essential for the regulation of a critical physiological process such as ovulation and provide new strategies for manipulation of fertility.