The expression of intercellular gap junctions during ovarian follicular development and atresia.

Abstract

In an ovarian follicle, the granulosa cells and oocyte are interconnected by vast numbers of gap junctions. These intercellular junctions permit the diffusion of metabolites, second messengers, and other molecules of less than 1000 daltons to be transferred from one cell to the cytoplasm of a neighboring cell. Intercellular communication via gap junctions is likely an important mechanism within the ovary for regulating the growth and development of an ovarian follicle. The ovary expresses the connexin43 (c43) type of gap junction. Using in situ hybridization and immunocytochemistry, we examined the expression of the c43 mRNA and protein during ovarian follicular development and atresia. Expression of the c43 gap junction gene was examined throughout the estrous cycle of the rat. c43 mRNA and protein are highly abundant in the granulosa cells of healthy developing pre-antral and antral follicles. Following the LH surge, the c43 mRNA and protein is greatly reduced only in the preovulatory follicles in preparation for the expulsion of the cumulus-oocyte complex from the ovary. Very little c43 mRNA and protein are detected in theca cells, corpora lutea, and atretic follicles. To examine the onset of atresia, immature rats were treated with estradiol to induce follicular development. After 48 hours the estradiol was withdrawn to induce atresia, and the expression of c43 mRNA and protein was examined. As early as 6 hours following estradiol withdrawal, the proportion of follicles undergoing atresia was increased, and the expression of c43 mRNA and protein was greatly lowered in those follicles. The phenomenon of atresia is an all-or-none process in that the entire follicle undergoes atresia or continues developing. Intercellular communication via gap junctions may play a role in coordinating this process of atresia. In conclusion, the level of c43 gap junction gene expression undergoes dramatic changes in preovulatory follicles following the LH surge, and early in the process of atresia. Therefore, this suggests that intercellular communication via gap junctions plays an integral role in regulating ovarian follicular growth and development.