Recombinant FSH (Org32489) induces follicle growth and ovulation in the adult cyclic rat

The effects of a single injection of recombinant human FSH (rhFSH; Org32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioestrus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ovulation rate on the day of expected oestrus. However, an additional, precocious ovulation resulting in a normal number of corpora lutea (13.3 ± 0.4, n = 6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vaginal plugs the next morning, was observed at this ovulation. Follicle counts showed a loss of large antral follicles due to ovulation and increased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as well as additional recruitment of new antral follicles. The endogenous serum FSH concentration on the subsequent day of oestrus (65 h after the rhFSH injection) as well as recruitment of small antral follicles were lower in the rhFSH-treated rats than in saline-treated controls. The ovulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group. Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH preparation (i.e. metrodin). Furthermore, the direct induction of ovulation by rhFSH or metrodin could not be prevented by the injection of an LHRH antagonist. It was concluded that rhFSH can induce acute ovulation in rats, and stimulates follicular development directly or indirectly through increased FSH levels after ovulation. It induces antral follicle growth and decreases early atresia in small antral follicles.