Sex Differences in Hypertension Risk: Insights from Placental Genomics and Pregnancy-Driven Vascular Programming

Abstract

The prevalence, pathogenesis, and long-term consequences of hypertension differ significantly across the sexes, and pregnancy is a special physiological stress test that can reveal a woman's underlying cardiovascular sensitivity. In addition to being direct risks to the health of the mother and fetus, hypertensive disorders of pregnancy (HDPs), especially preeclampsia, are also reliable indicators of future hypertension and cardiovascular disease in those who are afflicted. Fetal sex has a substantial impact on maternal vascular adaptation, according to new data from placental transcriptomics and epigenetics. This may be due to variations in the expression of angiogenic, immunomodulatory, and vasoactive genes. Sex-specific patterns of placental function, inflammation, and endothelium control are specifically influenced by X-linked gene dosage, escape from X-inactivation, and sex chromosomal composition. These biological variations highlight the placenta's potential function as a mediator and indicator of maternal cardiovascular risk, and they may help to explain why the incidence and severity of hypertensive pregnancy challenges vary depending on the fetal sex. The purpose of this review is to summarize the state of the art regarding how placental genetics and fetal sex influence maternal hypertensive risk both during and after pregnancy. Additionally, it will investigate how these findings may influence sex-specific cardiovascular screening, prediction, and prevention methods.

Keywords: X-linked genes; epigenetics; hypertensive disorders of pregnancy; placental genomics; sex differences.