Infertility in Superovulated Immature Rats: Role of Ovarian Steroid Hypersecretion12

Abstract

Immature rats superovulated with pregnant mare''s serum gonadotropin (PMSG) were ovariectomized at various times after mating and received various steroid replacement regimes to investigate the role of ovarian steroids in the etiology of the infertility which occurs in superovulated rats. Control (4 IU PMSG) and superovulated (40 IU PMSG) rats were allowed to mate on the night of day 1 and were killed on day 9, or allowed to mate on the night of day 2 and were killed on day 10. All ovariectomized rats received a daily regime of steroid injections which permitted a high rate of pregnancy on day 10 in control rats ovariectomized at 1000-1200 h on day 3. Implantation failed to occur in all superovulated rats which were not ovariectomized. Five of 11 superovulated rats which mated on the night of day 1 and were ovariectomized at 1000-1200 h on day 2 (day 1 of pregnancy) were pregnant on day 9 (7.2 .+-. 2.4 implantation sites, weighing 21.6 .+-. 1.3 mg in pregnant animals). Similarly, 12 of 25 superovulated rats which mated on the night of day 2 and were ovariectomized at 1000-1200 h on day 3 (day 1 of pregnancy) were pregnant on day 10 (10.3 .+-. 2.3 implantation sites, weighing 26.2 .+-. 0.8 mg in pregnant animals). Delaying the time of ovariectomy in superovulated rats which mated on the night of day 2 until 2200-2400 h on day 3 or 1000-1200 h on day 4 decreased the pregnancy rate (8/15 and 2/17, respectively) and the number of implantation sites and implantation site weight in pregnant animals (4.4 .+-. 0.6 and 1.5 .+-. 0.5; and 17.2 .+-. 1.2 mg and 13.7 .+-. 1.5 mg, respectively). Administration of estradiol at the time of ovariectomy and at 12 h intervals over the next 24 h reversed the beneficial effect of ovariectomy in a dose-related manner, both on the number of animals which remained pregnant and the number of implantation sites per pregnant animal. At least a large proportion of the embryos present in superovulated rats during the first 36 h after the time of mating are normal, and the consistent failure of implantation in intact rats results from abnormal ovarian hormone secretion after the time of fertilization, most probably from the hypersecretion of estrogens.