Pregnant nulliparous adolescents are at increased risk, inversely proportional to their age, of major obstetric syndromes, including preeclampsia, fetal growth restriction, and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, possibly compounded by sociodemographic factors associated with teenage pregnancy. The endometrium in most newborns is intrinsically resistant to progesterone signaling, and the rate of transition to a fully responsive tissue likely determines pregnancy outcome during adolescence. In addition to ontogenetic progesterone resistance, other factors appear important for the transition of the immature uterus to a functional organ, including estrogen-dependent growth and tissue-specific conditioning of uterine natural killer cells, which plays a critical role in vascular adaptation during pregnancy. The perivascular space around the spiral arteries is rich in endometrial mesenchymal stem-like cells, and dynamic changes in this niche are essential to accommodate endovascular trophoblast invasion and deep placentation. Here we evaluate the intrinsic (uterine-specific) mechanisms that predispose adolescent mothers to the great obstetrical syndromes and discuss the convergence of extrinsic risk factors that may be amenable to intervention
