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. / Thesis / Doctor of Philosophy (PhD)

<p> Early pregnancy in mammals can be disrupted by numerous stimuli. In particular, exposure to males which did not sire the litter disrupts early pregnancy in previously inseminated female mice. This is known as the Bruce effect. Evidence suggests that this effect is mediated by chemical emissions (pheromones) from the males. Castration of the males eliminates the effect whereas testosterone replacement restores it. This has suggested that androgen-dependent male accessory glands might be responsible. In particular, the preputial, vesicular and coagulating glands seem likely candidates for subserving the Bruce effect since they have been implicated in a variety of social behaviors.</p> <p> In these experiments, inseminated females were each housed below either 1) two males which had undergone preputial gland removal or, 2) two males which had undergone vesicular-coagulating gland removal or, 3) two males which had undergone preputial, vesicular and coagulating gland removal or 4) two males which had undergone sham surgery. In each case, males which had undergone gland removal disrupted pregnancy in inseminated females to the same extent as did intact males. Histology showed no regeneration of the glands. These results suggest that none of these major androgen-dependent male accessory glands is responsible for pheromonal emissions involved in the Bruce effect.</p> / Thesis / Master of Science (MSc)

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Abstract Objectives: The objective of this study was to determine if an association exists between prior induced and prior spontaneous pregnancy termination (PIPT and PSPT) and preterm birth (PTB) of first live births in Virginia. Methods: Data was collected by linking maternal data from Virginia’s live birth and fetal death registries. All first live, singleton births occurring in Virginia from 2000-2007 were analyzed. Logistic regression models that controlled for various demographic, medical and obstetric history factors were used to determine associations among prior pregnancy termination types. Results: Compared with women who had no history of previous pregnancy terminations, women who had 1 (OR = 1.1, 95% CI 1.31, 1.53), 2 (OR = 1.2, 95% CI 1.12, 1.24) and 3 or more (OR = 1.4, 95% CI 1.07, 1.13) total prior pregnancy terminations had an increased odds of experiencing PTB. Increased odds of PTB were found for women who had 2 (OR = 1.1, 95% CI 1.05, 1.18) and 3 or more (OR = 1.3, 95% CI 1.39, 1.61) PIPTs. Women who reported 1, 2, 3 or more PSPT had PTB odds-ratios of 1.4 (95% CI 1.37, 1.50), 1.7 (95% CI 1.48, 1.98) and 3.0 (95% CI 2.09, 4.22) times, respectively. Conclusion: Two or more PIPT and one or more PSPT were found to be a significant risk factor for PTB of a first live birth in Virginia, and women having 3 or more PSPT had three times the odds of experiencing this outcome. Health practitioners should take this data into account to target research, education and action strategies to those high risk groups of women associated with obtaining induced terminations and to those women more susceptible to spontaneous termination of pregnancy.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.