Sex differences in offspring of preeclamptic pregnancies

Abstract

A poor uterine environment causes changes in fetal development that affect the health of offspring long-term. Although there are multiple pathways that contribute to the development of cardiovascular and neurological disease, low birth weight or fetal growth restriction (FGR) predisposes offspring to these diseases. There is a link between fetal exposure to adverse influences and hypertension later in life. Many epidemiological studies support the link between fetal life and the risk of disease later in life. Experimental models have sought to provide mechanistic proof of this link while simultaneously investigating potential therapeutics or treatment pathways. Preeclampsia (PE), one of several hypertensive disorders in pregnancy, is a leading cause of morbidity and mortality for both the mother and fetus. Studies have shown that PE is a state of chronic inflammation and there is an imbalance between pro-inflammatory and regulatory immune cells and mediators. There is no cure for PE beyond the delivery of the fetal–placental unit, and many PE pregnancies result in FGR and preterm birth. Epidemiological data demonstrate that the sex of the offspring is correlated with the degree of cardiovascular disease that develops with the age of the offspring, yet few studies examine the effect of sex on the development of neurological disorders. Even fewer studies examine the effects of therapeutics on offspring of different genders following a PE pregnancy. Moreover, there remain significant gaps in knowledge concerning the role the immune system plays in FGR offspring developing hypertension or neurovascular disorders later in life. Therefore, the purpose of this review is to highlight current research on sex differences in the developmental programming of hypertension and neurological disorders following a PE pregnancy.