Lengthening the Bovine Estrous Cycle with Low Levels of Exogenous Progesterone: A Model for Studying Ovarian Follicular Dominance*

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Abstract
In cattle the development of ovarian follicles .gtoreq.5 mm occurs in waves, with either two or three waves per estrus cycle. To increase our understanding of the control of follicular dynamics in cattle, the present study was designed to characterize the pattern of follicular development during artificially lengthened estrous cycles. Cycles were lengthened by intravaginal insertion of Silastic devices containing progesterone [Controlled Internal Drug Release devices (CIDRs)]. Control heifers (group 1) received blank devices, whereas treated heifers received one (group 2) or two CIDRs (group 3) from days 14 to 28 after estrus. In groups 2 and 3, the insertion of CIDRs prevented return to estrus at the normal time and increased cycle length as compared to the control group (30.0 .+-. 0.0 and 31.0 .+-. 0.3 vs. 21.0 to 0.7 days, respectively, P < 0.05). After natural luteolysis and between days 22 and 28 of cycle, progesterone concentrations were maintained at lower levels in group 2 (range = 0.9-2.1 ng/ml) than in group 3 (range = 3.7-4.9 ng/ml, P < 0.003). Follicular development and regression were monitored daily by ultrasonography. The number of follicular waves per cycle was identical in groups 1 and 2 (2.7 waves per cycle), despite the significantly longer cycles in group 2. In group 2, the presence of one CIDR altered the normal pattern of follicular development by promoting the prolonged growth of the ovulatory follicle, and associated with it, a complete absence of follicular recruitment. When compared to ovulatory follicles in controls (group 1), ovulatory follicles in group 2 were detected on the ovaries for a longer time (1.8-fold), reached a greater maximal size (1.4-fold), and were dominant for a longer time (3-fold). Heifers in group 3 had significantly more follicular waves per cycle than groups 1 and 2 (3.8 vs. 2.7 waves per cycle, respectively, P < 0.05), due to the production of additional follicular waves during the lengthened cycle in three of six heifers. The other three heifers in group 3 showed patterns of follicular development similar to those of group 2. All heifers in the control group had normal preovulatory rises in estradiol and LH. During the period of treatment (days 14-28), 17.beta.-estradiol concentrations were higher in heifers in group 2 (lower progesterone levels) than in heifers in group 3 (higher progesterone levels; P < 0.0001). No differences were observed in basal LH concentrations between groups 2 and 3. In conclusion, this study shows that subtle changes in the hormonal mileu can dramatically alter the normal pattern of follicular development in cattle. Because lengthening the luteal phase with low levels of progesterone (1-2 ng/ml) promotes the prolonged development of dominant follicles, we propose that this approach could be used as a model to study potential regulators of follicular dominance.

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