The development of follicular cysts has been detected in numerous mammalian species, including humans, suggesting that this reproductive abnormality may be due to an underlying physiological pathway that is fairly ubiquitous in mammals. The research in this proposal focuses on the physiology that underlies the development of large follicular cysts. The cow has been chosen as the animal model for studies of this abnormality because follicular cysts are fairly common in this species and have been extensively described in previous research. In addition, the cow is a mono-ovulatory species and has been a useful animal model for understanding follicular development particularly because key follicular events (follicular selection, ovulation) occur at similar follicular diameters in humans and cows. The studies in this proposal test a working model based on previous scientific research, as well as our recent studies on the physiology that underlies the development of follicular cysts. This model predicts that during each estrous cycle, the normal estradiol surge induces a physiological condition that resembles the condition that results in follicular cysts. However, this """"""""physiological lesion"""""""" is removed by the increase in circulating progesterone following ovulation. This model is very appealing because it provides a generalized physiological explanation for the development of large follicular cysts. It may also provide an explanation for the varied clinical, environmental, and experimental situations that result in the development of follicular cysts as well as provide a rationale basis for the treatment of this disorder. However, it is prudent to test whether this physiological model has experimental validity prior to extensive studies on the specific cellular and molecular mechanisms that underlie this disorder or extrapolation of this working model into species other than the cow. Therefore, we propose two specific objectives that will use the bovine animal model to test whether a normal endogenous estradiol surge will result in the postulated physiological condition. Specific Objective I. Determine whether follicular cysts will develop following an endogenous estradiol and GnRH surge if the LH surge is blocked with a GnRH antagonist. Specific Objective II. Determine whether follicular cysts will develop following an endogenous estradiol, GnRH, and LH surge if the freshly ovulated follicle (corpus hemmoragicum) is removed.
