Myers Michelle, Middlebrook Brooke S, Matzuk Martin M, Pangas Stephanie A
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dev Biol. 2009 Oct 15;334(2):458-67. doi: 10.1016/j.ydbio.2009.08.001. Epub 2009 Aug 8.
Targeted disruption of the inhibin alpha gene (Inha(-)(/)(-)) in mice results in an ovarian phenotype of granulosa cell tumors that renders the animals infertile. Little is known about the reproductive defects prior to tumor development. Here, we report novel data on early follicle dynamics in Inha(-)(/)(-) mice, which demonstrate that inhibin alpha has important consequences upon follicle development. Morphological changes in both germ and somatic cells were evident in postnatal day 12 ovaries, with Inha(-/-) mice exhibiting numerous multilayered follicles that were far more advanced than those observed in age-matched controls. These changes were accompanied by alterations in follicle dynamics such that Inha(-/-) ovaries had fewer follicles in the resting pool and more committed in the growth phase. Absence of inhibin alpha resulted in advanced follicular maturation as marked by premature loss of anti-Müllerian hormone (AMH) in secondary follicles. Additionally, gene expression analysis revealed changes in factors known to be vital for oocyte and follicle development. Together, these data provide key evidence to suggest that regulation of the inhibin/activin system is essential for early folliculogenesis in the prepubertal mouse ovary.
小鼠抑制素α基因的靶向破坏（Inha-/-）导致卵巢颗粒细胞瘤表型，使动物不育。关于肿瘤发生前的生殖缺陷知之甚少。在这里，我们报告了关于Inha-/-小鼠早期卵泡动态的新数据，这些数据表明抑制素α对卵泡发育具有重要影响。出生后第12天的卵巢中，生殖细胞和体细胞均出现明显的形态学变化，Inha-/-小鼠表现出大量多层卵泡，其发育程度远高于年龄匹配的对照组。这些变化伴随着卵泡动态的改变，使得Inha-/-卵巢中静止池中的卵泡数量减少，而处于生长阶段的卵泡数量增加。抑制素α的缺失导致卵泡提前成熟，表现为次级卵泡中抗苗勒管激素（AMH）过早丢失。此外，基因表达分析揭示了已知对卵母细胞和卵泡发育至关重要的因子的变化。总之，这些数据提供了关键证据，表明抑制素/激活素系统的调节对于青春期前小鼠卵巢的早期卵泡发生至关重要。
