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Biology of Reproduction, Vol 50, 336-348, Copyright © 1994 by Society for the Study of Reproduction
ARTICLES |
JF Wiesen and AR Midgley Jr
Reproductive Sciences Program, National Center for Infertility Research, University of Michigan, Ann Arbor 48109.
The process of atresia is an all-or-none phenomenon in that an entire follicle either undergoes atresia or continues along the developmental pathway. The absence of pockets of atresia adjacent to healthy areas of granulosa cells suggests the existence of a coordinating influence within the entire follicular unit during the process of atresia. Gap junctions interconnect the granulosa cells and the oocyte in the ovarian follicle, forming a metabolic syncytium. Intercellular communication provided via the gap junctions may play a role in coordinating the process of atresia. This study addresses the potential hormonal regulation of the gap junction gene during the process of atresia. Immature female rats were given an estradiol (E2) implant to induce follicular development, and after 48 h the E2 was withdrawn to induce atresia. The ovary is an extremely heterogeneous tissue with multiple cell types and many follicles at different stages of development. Therefore, in situ hybridization and immunocytochemistry were ideal techniques to localize gap junction gene expression precisely to specific cells in the ovary. Observations resulting from these studies revealed that while the granulosa cells of healthy, developing, pre-antral and antral follicles expressed large amounts of connexin 43 (cx 43) gap junction mRNA and protein, this expression was greatly reduced in atretic follicles. In the follicles undergoing atresia, the levels of cx 43 gap junction mRNA and protein were reduced as early as 6 h after the withdrawal of E2. The levels of cx43 mRNA and protein continued to decrease as atresia progressed, and at 11 h after withdrawal of E2 very little cx43 mRNA or protein was seen. These results indicate that gap junction mRNA and protein are decreased in association with atresia and support the hypothesis that a loss of gap junctional communication plays a coordinating role in the process of atresia.
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