Pregnancy stage determines the effect of chronic stress on ovarian progesterone synthesis.

Stress-induced glucocorticoid release is thought to be a primary driver by which maternal stress negatively impacts pregnancy outcomes, but the neuroendocrine targets mediating these adverse outcomes are less well understood. We hypothesized that stress-induced glucocorticoid secretion influences pituitary hormone secretion, resulting in altered ovarian progesterone synthesis. Using a chronic restraint model of stress in mice, we quantified pituitary hormones, steroid hormone production, and expression of ovarian genes that support progesterone production at both early- (day 5) and mid-pregnancy (day 10). Females subjected to daily restraint had elevated baseline corticosterone during both early- and mid-pregnancy. However, lower circulating progesterone was observed only during early pregnancy. Lower progesterone production was associated with lower expression of steroidogenic enzymes in the ovary of restrained females during early pregnancy. There were no stress-related changes to luteinizing hormone (LH) or prolactin (PRL). By mid-pregnancy, circulating LH decreased regardless of treatment, and this was associated with down-regulation of ovarian steroidogenic gene expression. Our results are consistent with a role for LH in maintaining steroidogenic enzyme expression in the ovary, but neither circulating PRL nor LH were associated with the stress-induced inhibition of ovarian progesterone production during early pregnancy. We conclude that chronic stress impacts endocrine networks differently not only in pregnant and non-pregnant mammals, but also in different stages of pregnancy.