Simon A M, Goodenough D A, Li E, Paul D L
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1997 Feb 6;385(6616):525-9. doi: 10.1038/385525a0.
The signals regulating ovarian follicle development and the mechanisms by which they are communicated are largely undefined. At birth, the ovary contains primordial follicles consisting of meiotically arrested oocytes surrounded by a single layer of supporting (granulosa) cells. Periodically, subsets of primordial follicles undergo further development during which the oocyte increases in size and the granulosa cells proliferate, stratify and develop a fluid-filled antrum. After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum. It has been proposed that intercellular signalling through gap junction channels may influence aspects of follicular development. Gap junctions are aggregations of intercellular channels composed of connexins, a family of at least 13 related proteins that directly connect adjacent cells allowing the diffusional movement of ions, metabolites, and other potential signalling molecules. Here we show that connexin 37 is present in gap junctions between oocyte and granulosa cells and that connexin 37-deficient mice lack mature (Graafian) follicles, fail to ovulate and develop numerous inappropriate corpora lutea. In addition, oocyte development arrests before meiotic competence is achieved. Thus, cell-cell signalling through intercellular channels critically regulates the highly coordinated set of cellular interactions required for successful oogenesis and ovulation.
调节卵巢卵泡发育的信号及其传递机制在很大程度上尚不清楚。出生时，卵巢含有原始卵泡，这些卵泡由减数分裂停滞的卵母细胞组成，周围环绕着单层支持（颗粒）细胞。原始卵泡的亚群会定期进一步发育，在此过程中，卵母细胞体积增大，颗粒细胞增殖、分层并形成充满液体的卵泡腔。排卵后，卵母细胞恢复减数分裂，卵泡中保留的颗粒细胞分化为类固醇生成细胞，形成黄体。有人提出，通过间隙连接通道的细胞间信号传导可能会影响卵泡发育的各个方面。间隙连接是由连接蛋白组成的细胞间通道聚集体，连接蛋白是一个至少由13种相关蛋白质组成的家族，它们直接连接相邻细胞，允许离子、代谢物和其他潜在信号分子进行扩散运动。在这里，我们表明连接蛋白37存在于卵母细胞和颗粒细胞之间的间隙连接中，并且连接蛋白37缺陷型小鼠缺乏成熟（格拉夫）卵泡，无法排卵并形成大量异常黄体。此外，卵母细胞发育在达到减数分裂能力之前就会停滞。因此，通过细胞间通道的细胞间信号传导对成功的卵子发生和排卵所需的高度协调的细胞间相互作用起着关键的调节作用。
