Estrogen–progesterone balance in the context of blastocyst implantation failure induced by predator stress

Diverse stressors can disrupt blastocyst implantation in inseminated female mammals. Stress-induced implantation failure can be mimicked by minute doses of exogenous estradiol, and some evidence indicates that it may be mitigated by exogenous progesterone. In Experiment 1, we showed that acute exposure to a rat across a wire-mesh grid caused elevation of corticosterone and progesterone. In Experiment 2, we showed that exposure of inseminated mice to rats across a grid during gestation days 1-5 was associated with avoidance of proximity to the grid and a significantly reduced number of implantation sites on gestation day 6. Rat-exposure also resulted in elevated progesterone levels in females that maintained their pregnancies, and elevated estradiol levels in females that lost their pregnancies. In Experiment 3, we investigated whether exogenous progesterone, estradiol, or a combination of both could influence implantation failure induced by rat-exposure stress. Treatment with 100 ng estradiol per day on gestation days 1-5 induced a complete absence of implantation sites on gestation day 6, regardless of the presence or absence of the stressor. Administration of 500 μg progesterone per day was insufficient to prevent the stress-induced pregnancy loss. However, 500 μg progesterone plus 10 ng estradiol per day did prevent implantation failure in rat-exposed females. These findings are consistent with the hypothesis that estradiol elevations contribute to stress-induced pregnancy loss, but show paradoxically that low doses of estradiol can act together with progesterone to mitigate stress-induced pregnancy loss.