The control of estradiol and progesterone secretion by TGF-beta in bovine ovarian follicles

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One of the major limiting factors in the production of embryos from cattle of high genetic merit is the variable number of recruited follicles following a standard superovulatory hormone treatment resulting in poor ovulation rates. A better understanding of the role of locally produced and circulating hormones in normal ovarian follicle development is necessary to resolve this problem. In cattle, antral follicle development from 1 to 4 mm is dependent on the action of pituitary hormones (FSH,LH); metabolic factors (IGF, insulin); and locally produced ovarian growth factors of the TGF-ß superfamily. These factors must be present to stimulate the production of estradiol which is a key hormone involved in follicle growth.  Once the follicles have reached the 4 mm threshold, they embark in a fast-growth phase lasting 5-6 days where selection of a single dominant ovulatory follicle occurs. We have shown that TGF-ß1 has multifunctional effects and can either stimulate or inhibit estradiol production by granulosa cells of the developing follicle. The objective of this research program is to understand if and how TGF-ß1 can act as a survival factor that limits proliferation and slows down follicle growth while maintaining the granulosa cell viable, and how TGF-B1 inhibits FSH-induced production of estradiol and progesterone. This will be achieved using molecular biology techniques with an in vitro model of cultured bovine granulosa cells. A better understanding of the role of TGF-ß1 and related molecules will be important to increase the pool of follicles that can respond to FSH in order to improve superovulatory response. This research is also relevant to find new ways to prevent and correct infertility problems associated with ovarian inactivity.