Is there a role for placental senescence in the genesis of obstetric complications and fetal growth restriction?

Abstract

The placenta ages as pregnancy advances, yet its continued function is required for a successful pregnancy outcome. Placental aging is a physiological phenomenon; however, there are some placentas that show signs of aging earlier than others. Premature placental senescence and aging are implicated in a number of adverse pregnancy outcomes, including fetal growth restriction, preeclampsia, spontaneous preterm birth, and intrauterine fetal death. Here we discuss cellular senescence, a state of terminal proliferation arrest, and how senescence is regulated. We also explore the role of physiological placental senescence and how aberrant placental senescence alters placental function, contributing to the pathophysiology of fetal growth restriction, preeclampsia, spontaneous preterm labor/birth, and unexplained fetal death.

Keywords: DNA damage; aging; cellular senescence; cyclin-dependent kinase; fetal death; fetal growth restriction; mammalian target of rapamycin complex; membrane rupture; mitogen-activated protein kinase; oxidative stress; p16; phosphoinositide 3-kinase; placental aging; preeclampsia; preterm birth; preterm labor; reactive oxygen species; senescence-associated beta-galactosidase; senescence-associated heterochromatin foci; senescence-associated secretory phenotype; small for gestational age; stillbirth; telomere; tumor suppressor protein p53.