P-593 developmental programming by maternal androgen excess is mediated by androgen receptor pathways

Abstract Study question How does maternal hyperandrogenism featured PCOS-pregnancy affects the placental and embryo development further contributes to of PCOS-like phenotypes in adult offsping? Summary answer Maternal compromises due placenta dysfunction, leading subsequent anxiety-like behavior and/or impaired metabolism offspring What is known already Women with PCOS suffer an increased risk having miscarriage, preterm delivery, perinatal mortality. The hostile utero environment because likely play a detrimental role as well disease susceptibility later life. As according previous findings, daughters women have 5 fold getting diagnosis, while sons from metabolic diseases. design, size, duration We used mouse model induced by continuous exposure dihydrotestosterone (DHT) prepuberty, which developed obesity, anovulation, abnormal ovarian morphology study effects during pregnancy. In comparison, we also simultaneously treated females flutamide, androgen-receptor blocker. examined embryos at E10.5 E13.5 focusing on placentas relation development. Their male female phenotyped until 6 months age. Participants/materials, setting, methods To explore molecular mechanisms contributing developmental defects, whole genome bisulfite bulk RNA sequencing were performed. Human Trophoblast organoid culture under different conditions was applied evaluate hyperandrogetism With help trophoblast system, possible treatment options are going be explored. Main results chance found lower pregnancy rate together defective embryonic development, partially prevented when co-treated androgen receptor blocker, flutamide. revealed that DHT severely interferes fetal addition, DHT-exposed dams showed differentiation capacity cell types located labyrinth. hyperandrogenic led partial disturbance effect still investigation. Limitations, reasons for caution Although pathway responsible abnormalities phenotypes, flutamide most unfavorable effects, use clinic tightly regulated not suggested PCOS. Wider implications findings greatly offspring. Such mainly mediated administration prevents compromised Trial registration number applicable