Induction of apoptosis in equine chorionic gonadotropin (eCG)-primed rat ovaries by anti-eCG antibody.

We have established a model to examine the early events of apoptosis in small antral follicles in vivo. Immature female rats injected with 15 IU eCG, and subsequently (24 h later) with an anti-eCG antibody to induce gonadotropin withdrawal, displayed a significantly lower ovarian weight and increased incidence of follicular atresia and granulosa cell death, especially in small- to medium-sized follicles. Evidence of apoptosis was apparent in a significantly higher proportion of granulosa cells from antibody-treated rats, which exhibited membrane blebbing, nuclear and cytoplasmic condensation, fragmentation, and phagocytosis. In addition, there was a loss of the regular organization of the lamina densa in the follicular basement membrane. Degradation of DNA was consistently found by 24 h in the antibody-treated group, and ladders could be observed as early as 1 h after treatment. Although cell death was observed after antibody treatment in some larger antral follicles, the occurrence of apoptosis was less frequent. These results demonstrate that gonadotropin withdrawal in vivo rapidly induces apoptosis in small- to medium-sized antral follicles at the critical stage of development when atresia is commonly observed, suggesting that this model is ideal for studying apoptosis in the ovary.