Early pregnancy disruption in mice (the Bruce effect): The role of sexual satiety, castration, and excreted steroids of novel males

Abstract

<p>Early pregnancy in mammals is vulnerable to various environmental factors, one of which is exposure to novel males (the Bruce effect). It is well established that androgen-dependent chemical excretions from novel male mice prevent ovoimplantation in proximate previously-inseminated females. The chemical nature of these pheromones has not been determined. This thesis explores the role of steroids in the Bruce effect after castration and sexual satiety and also analyzes excreted steroids released by novel males. Experiments 1 and 2 demonstrated that recent sexual experience can reduce novel males' capacity to disrupt pregnancy. Novel males were allowed to mate with stimulus females prior to exposure to inseminated females during the implantation period. Unmated males disrupted pregnancy more often than did mated males. Experiment 3 was designed to examine the time course of males' ability to disrupt pregnancy following castration. The probability of retention of pregnancy increased as a linear function of time since castration. Castrated males continued to disrupt pregnancy during the initial weeks after surgery, but by 6 weeks, the majority of females remained pregnant. Males' excretion of testosterone and 17β-estradiol in urine, measured via ELISA procedures, diminished gradually during the weeks after castration. In Experiments 4 and 5, the concentrations of urinary steroids from novel males were measured during exposure to inseminated females. These studies revealed that males' urinary excretions of testosterone and 17β-estradiol correlated with females' pregnancy loss. Also, males excreted higher concentrations of 17β-estradiol but not testosterone when exposed to females on day 3 of pregnancy compared to when males were isolated. In Experiment 6, steroids were applied to the nasal region of recently inseminated females. Nasal application of testosterone propionate did not disrupt pregnancy. However, topical application of either 17β-estradiol or 17β-estradiol benzoate completely prevented implantation at very low doses. Results from these studies suggest that steroids play an important role in novel-male-induced pregnancy disruption. As endogenous levels of androgens are diminished, either through castration or sexual satiation, novel males' ability to disrupt pregnancy decreases. Furthermore, novel males' urine contains 17β-estradiol, the quantity of which rises during exposure to inseminated females. Also, this steroid can disrupt pregnancy through nasal application on the female. Levels of 17β-estradiol are known to be elevated in females experiencing early pregnancy disruption. Thus, 17β-estradiol may be a potential pheromone involved in the Bruce effect.</p>