Steroid receptors and coregulators in ovarian follicles of cows with induced cystic ovarian disease.

HUGO H. ORTEGA; NATALIA S. ALFARO; MELISA M.L. VELAZQUEZ; AYELEN N. AMWEG; NATALIA R. SALVETTI

Workshop; US-South America Workshop in Neuroendocrinology; 2011

Cystic ovarian disease (COD) is an important cause of infertility in cattle and although it is known that the main components of the ethio-pathogenesis of COD are related to the hypothalamus?pituitary?ovarian axis, the follicular persistence is related to intraovarian factors. Ovarian folliculogenesis is a complex cascade of events and locally produced steroids play a key role in the growth, differentiation and function of ovarian follicles. Steroids hormones act through specific receptors inducing the expression of specific gene networks involved in regulating the differentiation and growth of reproductive tissues. Also, several co-activator and co-repressor proteins have been identified, which are implicated in mechanisms of transcriptional activation and repression mediated by steroids. The aim of the present study was to determine the expression of steroid receptors (progesterone receptor: PR; estrogen receptor alfa: ER-alfa and estrogen receptor beta: ER-beta), co-acivators (steroid receptor coactivator 3: SRC-3) and co-repressors (repressor of estrogen receptor activity: REA and  silencing mediator for retinoic acid and thyroid hormone receptor: SMRT) in ovarian follicular structures of cows with induced COD compared with regularly cycling cows by immunohistochemistry. Ten animals were synchronised in their estral cycles and five were then subject to the induction of COD by administration of ACTH and five were used as control to obtain preovulatory follicles. The immunoexpression was evaluated in follicular wall of secondary, tertiary, atretic, and cystic follicles. The follicular cysts presented a similar expression of ER-alfa that tertiary follicles of both groups and significantly higher than secondary and atretic follicles. The expression of ER-beta in the granulosa cell layer was higher in tertiary than in secondary and atretic follicles in control animals and in cystic follicles of induced COD. Theca cells were scarcely stained in the two groups, but cystic follicles were less stained than tertiary follicles from control animals. Not differences were evidenced in PR between control and COD groups. The expression of SRC-3 was observed in granulosa and theca of all follicles categories with a significantly increase in theca interna of cystic follicles. REA was localized in the granulosa and theca without differences in their expression. The granulosa of cyst showed a significantly higher expression of SMRT than other follicles categories. In summary, ovaries from animals with induced COD exhibited altered steroid receptor expression compared with normal animals, as well as changes in the expression of their regulators. It is reasonable to suggest that in conditions characterized by altered ovulation and follicular persistence, such as COD, changes in the intraovarian expression of these proteins could play a role in their pathogenia.