Endocrine Center of Okayama University Hospital, Okayama, Japan.
Mol Reprod Dev. 2011 Jan;78(1):9-21. doi: 10.1002/mrd.21265. Epub 2011 Jan 11.
The oocyte plays an important role in regulating and promoting follicle growth, and thereby its own development, by the production of oocyte growth factors that predominantly act on supporting granulosa cells via paracrine signaling. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-β (TGF-β) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15), in ovarian function. The identification of Bmp15 and Gdf9 gene mutations as the causal mechanism underlying the highly prolific or infertile nature of several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function. Similarly, large numbers of mutations in the GDF9 and BMP15 genes have been identified in women with premature ovarian failure and in mothers of dizygotic twins. The purpose of this article is to review the genetic studies of GDF-9 and BMP-15 mutations identified in women and sheep, as well as describing the various knockout and overexpressing mouse models, and to summarize the molecular and biological functions that underlie the crucial role of these two oocyte factors in female fertility.
卵母细胞通过旁分泌信号产生卵母细胞生长因子，对支持颗粒细胞起主要作用，从而在调节和促进卵泡生长以及自身发育方面发挥重要作用。在小鼠中的遗传研究表明，转化生长因子-β（TGF-β）超家族中的两种关键卵母细胞衍生生长因子，生长分化因子 9（GDF-9）和骨形态发生蛋白 15（BMP-15），在卵巢功能中起着关键作用。Bmp15 和 Gdf9 基因突变作为几个绵羊品种高产或不育的因果机制，其作用方式呈剂量依赖性，这也突出了这两个基因在卵巢功能中的关键作用。同样，在卵巢早衰的女性和双胞胎母亲中也发现了大量 GDF9 和 BMP15 基因突变。本文旨在综述在女性和绵羊中发现的 GDF-9 和 BMP-15 基因突变的遗传研究，以及描述各种基因敲除和过表达的小鼠模型，并总结这些两种卵母细胞因子在女性生育能力中发挥关键作用的分子和生物学功能。
