The Role of Steroids in Novel-Male Induced Pregnancy Disruptions in Mice (The Bruce Effect)

Abstract

Mammalian reproduction is vulnerable to psychological and physiological stress. This research focuses on the psychophysiological mechanisms that lead to the disruption of pregnancy by the failure of implantation of fertilized ova into the uterine walls. The underlying hormonal mechanisms of implantation failure are not well understood. It is known that many environmental events have a substantial impact on hormonal dynamics in mammals. These environmentally induced hormonal changes can disrupt implantation. This thesis focuses on the hormonal dynamics of female mice that lose their pregnancy when exposed to a novel male during the implantation period (the Bruce effect). In Study 1, a repeatable and reliable Bruce effect was established by indirectly exposing inseminated females during the implantation period to novel males housed above them separated by a wire grid floor. Separating the animals allowed for the independent study of the chemical transmission from male to female, and the physiological transduction within the female. The findings from this study suggest that females must come in direct contact with the excretions of the stimulus novel males. The more excretions the females encounter, the greater the chance is of pregnancy disruption. The Bruce effect is known to be dependent on androgens in the stimulus males, since castration eliminates their capacity to disrupt pregnancy. Study 2 showed that surgically removing the androgen-dependent preputial glands from the stimulus males does not diminish their capacity to disrupt pregnancy. Study 3 showed that administering 17β-estradiol to castrated males can restore their capacity to disrupt pregnancy. This suggests that 17β-estradiol as well as testosterone is involved in the chemical transmission of the Bruce effect. It has been hypothesized that 17β-estradiol is elevated in females that fail to implant in the presence of a novel male. Administering an antibody specific to 17β-estradiol to females during their implantation period can lower the hypothesized increase in 17β-estradiol and implantation takes place despite the exposure to novel males. Finally, in Study 4 testosterone, 17β-estradiol and its major metabolites the estrone conjugates were quantified in females' urine and feces while exposed to novel males during implantation. It was found that testosterone and 17β-estradiol were significantly elevated in females that failed to implant while exposed to novel males. In conclusion, this line of research reveals a potential role of steroids in novel male induced pregnancy disruptions in mice. Elevated testosterone and 17β-estradiol are shown to be related to the prevention of implantation in mice. These hormonal dynamics may be partially responsible for the physiological transduction of the Bruce effect.