Estradiol-induced adult anovulatory syndrome in female C57BL/6J mice: age-like neuroendocrine, but not ovarian, impairments

Abstract

Use of exogenous gonadotropin to induce ovulation may be associated with reduced fertility resulting from excessive follicular stimulation. To investigate this problem further a superovulatory dose of 40 IU PMSG was administered to 29-day-old rats at 0800-0900 h on Day -2 (see text footnote 4) of the experiment (SOV animals). Control rats received 4 IU PMSG, a dose which induces a physiological number of ovulations followed by a normal pregnancy. A volume of antiserum (a/s) known to inhibit completely the ovarian and uterine weight increasing capacity of 40 IU PMSG was injected i.p. at 1800 h on Day 0 to 50% of the SOV group (SOV a/s animals). Females were then caged with mature fertile males overnight, examined for evidence of mating on Day 1, and sacrificed at 1030-1230 h on Days 1-5. Tissue and blood were collected for steroid analyses, and oviducts and uteri were flushed to determine the number and location of embryos. Animals receiving a/s had higher embryo recovery on Days 4 and 5 compared with SOV animals. On Day 5 a mean of 10.5 embryos was recovered from SOV a/s animals compared with 8.2 in control rats and 2.4 in SOV animals. On Day 5 most SOV animals had no embryos whereas following a/s all animals were pregnant and the majority of embryos were in the uterus. In control rats all embryos were in the uterus on Day 5. Serum and ovarian progesterone levels were 3-4-fold higher in SOV animals compared with controls, but were unchanged by administration of a/s, whereas estradiol-17β in both serum and ovaries was drastically reduced to levels close to those observed in control rats within 18 h of administration of a/s. These results suggest that early embryo loss after superovulation may result, at least in part, from excessive estrogen secretion, probably arising from remaining follicles. This loss could occur through excessive stimulation of either the oviductal or uterine environments or both.