Ovary

Regulation of Prohibitin Expression During Follicular Development and Atresia in the Mammalian Ovary

Abstract
Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival. Prohibitin content is inversely associated with cell proliferation, but increases during granulosa cell differentiation, and in earlier events of apoptosis in a temperature-sensitive granulosa cell line. In this study we have characterized the spatial expression patterns for prohibitin, using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Comparative western blot analyses of granulosa cell lysates from control, equine chorionic gonadotropin (eCG)-primed, and eCG plus anti-eCG treated ovaries (gonadotropin withdrawal) were conducted. Prohibitin was immunolocalized in rat ovarian sections probed either with antibodies against proliferating cell nuclear antigen (PCNA), cholesterol side-chain cleavage cytochrome P-450 (P-450scc), or in in situ terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin end labeling (TUNEL) sections. Additionally, porcine oocytes, zygotes and blastocyts were also immunolocalized with prohibitin antibody. Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells and the oocyte. The results indicate that prohibitin protein expression in the gonadotropin-treated cells was upregulated. Immunoreactivity of prohibitin was inversely related to PCNA expression during follicular maturation and co-localized with P-450scc. Prohibitin appeared to be translocated from the cytoplasm to the nucleus in atretic follicles, germinal vesicle-stage oocytes, zygotes and blastocysts. These results suggest that prohibitin has several functional regulatory roles in granulosa and theca-interstitial cells, and in the ovum during follicular maturation and atresia. It is likely that prohibitin may play an important role in determining the fate of these cells and eventual follicular destiny.

Key words: Ovary • Apoptosis • Follicular development • Granulosa cells • Oocyte development

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