Effects of phenobarbital-induced ovulatory delay on the follicular population and serum levels of steroids and gonadotropins in the hamster: A model for atresia.

Abstract

A model was developed for the study of atresia of preovulatory follicles in the hamster. The effects of ovulatory delay on the ovarian follicular population, number of ova spontaneously ovulated, and serum concentrations of steroids and gonadotropins were assessed. This model was based on earlier observations of Everett and Sawyer (1950) who reported atresia of rat preovulatory follicles after 3 or 4 days of continued postponement of ovulation with sodium pentobarbital. Cyclic hamsters weighing 90-110 g were maintained on a 14L:1OD schedule (lights on at 0500 h). Ilamsters injected s.c. with 6.5 mg phenobarbital (Phen)/100 g BW at 1300 h on proestrus exhibited 1 day of ovulatory delay. Hamsters injected with 6.5 mg Phen at 1300 h on proestrus and also with 13 mg Phen at 1200 h the next day, exhibited a 2-day delay;an additional injection of 19.5 mg Phen at 1200 h on the following day was required for 3 days of ovulatory delay. Histological examination of the ovary revealed that the diameter of antral follicles on proestrus (561 ± 12pm) increased significantly after 1 day of ovulatory delay (680 ± 11 pm). After 2 days of ovulatory delay, no significant alteration of antral follicular diameter was observed; however, on Day 3 of ovulatory delay, the original set of preovulatory follicles exhibited early signs of atresia as evidenced by degenerating granulosa cells and by pyknotic nuclei within the oocytes. Interestingly, on Day 3 of delay a new set of small-diameter antral follicles (527 ± 22 pm) was observed, indicating that as the original set of preovulatory follicles became atretic they were gradually replaced by a new set of antral follicles. Unlike the rat after 3 days of barbiturate administration, the hamster ovulated 1.5 days later. This was due to the rapid recruitment of antral follicles as the original set became atretic. The number of ova shed after 2 (17.9 ± 0.4 ova) and 3 (19.1 ± 0.6 ova) days of delay (but not after 1-day delay, 12.5 ± 0.3 ova) was significantly higher than in untreated cyclic hamsters (11.3 ± 0.7 ova). The higher ovulation rate may have been the result of recruitment of stage V follicles observed only in delayed hamsters. Injections of Phen were required at 1200 h (1 hearlier tban the first injection) to cause 2 and 3