Maternal Anxiety Affects Embryo Implantation Via Impairing Adrenergic Receptor Signaling in Decidual Cells

Psychological stress is closely related to recurrent pregnancy failure (RPF) and infertility, but the mechanism is still unclear. The human endometrium plays a vital role in providing the site for embryo implantation; many factors have been implicated in unsatisfactory endometrial receptivity in RPF. In the current study, we found that women with pregnancy loss or infertility have a higher serum epinephrine level, indicating a potential correlation between psychological stress and pregnancy failure. RNA-sequencing of the tissues from endometrial receptive phase of the normal and embryo recurrent implantation failure (RIF) and discovered that stress hormones could affect the functional status of the receptive phase of the endometrium. Subsequent analysis showed that the epinephrine signaling acts as an important regulator of endometrial receptivity through PI3K-AKT and FOXO1 signaling pathways. We also found that patients with RIF have attenuated expression of alpha-2C-adrenergic receptor (ADRA2C), and its down regulation would inhibit the promotion of adrenergic signal-mediated decidualization. We treated the early pregnancy model of stressed mice and observed that they had high serum epinephrine levels, defective uterine adrenergic receptor expression and low pregnancy rates. All together, our findings indicate that mental stress during early pregnancy can alter the functional status of endometrial receptivity.