Functional androgen signaling pathway potentiates maternal-fetal interactions------ implantation, placentation and...

A growing body of evidence demonstrates that androgens play crucial roles in female reproductive physiology. Androgen receptor (AR) expression appears at all levels of the hypothalamic-pituitary-gonadal axis and other female reproductive organ or tissue such as uterus, placenta and immune system. Via AR-mediated mechanisms, androgens regulate key reproductive processes including follicular development, embryo implantation, placental formation, and pregnancy maintenance. AR knockout models suffer from considerable reproductive defects characterized by defective follicular development, reduced ovulation, decreased fertility, even premature ovarian failure. Clinically, low maternal serum testosterone correlates with diminished ovarian reserve and adverse pregnancy outcomes. These findings establish that a critical threshold of androgen is essential for successful pregnancy. While androgen excess has long been associated with follicular dysfunction and endometrial abnormalities leading to infertility and miscarriage, emerging evidence indicates that insufficient androgen similarly compromise female reproductive function. This review synthesizes fundamental discoveries and clinical evidence elucidating androgen's multifaceted effects on female reproduction. Collectively, we underscore the physiological significance of optimal androgen signaling and the pathological consequences from androgen deficiency across reproductive process.