Changes in expression of connexin 43 gap junction messenger ribonucleic acid and protein during ovarian follicular growth

Within the ovarian follicle, communication between granulosa cells and the oocyte via gap junction channels may be crucial for the determination of whether a given follicle continues its growth and development or becomes atretic. Numerous gap junction channels exist between granulosa cells and between the oocyte and granulosa cells. This study addresses the potential hormonal regulation of the gap junction gene during the processes of follicular growth, ovulation, and atresia. Because the ovary is an exceptionally heterogeneous tissue with numerous follicles at different stages of development, in situ hybridization and immunocytochemistry were used to localize gap junction gene expression precisely to specific cells in the ovary. The results demonstrated that only the granulosa cells of healthy, developing, preantral and antral follicles express large amounts of connexin 43 (cx43) gap junction messenger RNA (mRNA) and protein. Theca cells contained negligible levels of cx43 gap junction mRNA or protein. Very little cx43 gap junction mRNA or protein was detected in follicles undergoing atresia or in the corpora lutea. Additionally, during the night of proestrus, the level of cx43 gap junction mRNA and protein seen in the granulosa cells of the large preovulatory follicles dramatically decreased after the ovulatory surge of LH. This decrease was seen only in the preovulatory follicles and not in less-developed follicles, thereby demonstrating a differential response of the follicles to the preovulatory hormonal stimuli. Therefore, the expression of the gap junction gene may be hormonally regulated during follicular growth and development, in preovulatory follicles in preparation for ovulation, and during the process of atresia.