Greenfeld Chuck R, Roby Katherine F, Pepling Melissa E, Babus Janice K, Terranova Paul F, Flaws Jodi Anne
Department of Physiology, University of Maryland, Baltimore, Maryland 21201, USA.
Biol Reprod. 2007 Feb;76(2):224-31. doi: 10.1095/biolreprod.106.055509. Epub 2006 Oct 25.
It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, although this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary and an important regulator of folliculogenesis.
人们认为，在胚胎期和新生儿期会形成有限的原始卵泡库。出生时，小鼠卵巢由相互连接的卵母细胞簇组成，周围环绕着前颗粒细胞。出生后不久，这些结构，即生殖细胞囊肿或巢（GCN），会分解以促进原始卵泡的形成。肿瘤坏死因子α（TNF）是一种广泛表达且具有多种功能的蛋白质。TNF在卵巢中表达，可能调节大鼠的GCN分解。我们通过使用体外卵巢培养系统以及突变动物模型，研究了它是否参与小鼠的GCN分解和卵泡形成。我们发现TNF及其两种受体（TNFRSF1A和TNFRSF1B）在新生小鼠卵巢中表达，并且TNF在体外促进新生卵巢中的卵母细胞死亡。然而，任一受体的缺失均不影响卵泡储备，这表明TNF在体内并不调节GCN分解。Tnfrsf1b缺失导致卵泡生长明显加速以及原始卵泡数量随之增加。原始卵泡数量的这种增加似乎并非由于原始卵泡闭锁减少所致，尽管这一点不能完全排除。本研究表明，小鼠卵母细胞表达两种TNF受体，并且对TNF诱导的死亡敏感。此外，TNFRSF1B被证明是TNF在小鼠卵巢中功能的重要介质以及卵泡发生的重要调节因子。
