Placental epigenetic clocks: relations with in-utero exposures, ancestry, and fetal growth

Abstract

Placental aging is a normal physiologic phenomenon during pregnancy. However, premature aging of the placenta can lead to decreased functional capacity of the placenta and obstetric complications including preeclampsia, pre-term birth, still birth and fetal growth restriction. Routine methods used in aging studies such as histopathological examination of the placenta and telomerase homeostasis markers may not detect aging alterations that are subtle and caused by senescence-independent DNA damage. The field of biological aging has recently been revolutionized by molecular methods that estimate the “biological clock” of a tissue with high accuracy using DNA methylation markers. This talk will introduce ongoing work based on the concept of epigenetic age acceleration in placenta, demonstrating its relationship with genetic ancestry, maternal cardiometabolic risk factors, and in-utero exposures. In addition, data will be presented illustrating the potential that epigenetic aging of the placenta may be one of the mechanisms underlying sexually-biased fetal growth responses to adverse exposures. Lastly, the talk will outline potential research directions for facilitating the utility of placental epigenetic clocks for gaining novel insights on placental origins of pregnancy outcomes and childhood diseases, and for the discovery of biomarkers as indicators of high-risk pregnancy.