Early Placental Development and Disorders
Although many of the most vexing complications of human pregnancy, including sporadic and recurrent early pregnancy loss, preeclampsia, intrauterine growth restriction, molar pregnancies, and placenta accreta/increta/percreta likely have their origins in very early placental developmental abnormalities, our understanding of these abnormalities remains frustratingly limited. This deficit is inherent to the placenta because access to primary early human gestational tissues is very limited, for ethical and logistical reasons. Comparative placentation among mammalian species reveals the human placenta to be quite unique and limits the utility of animal modelling. In vitro models of human trophoblast differentiation are likewise limited by tissue access, spontaneous differentiation of primary trophoblast cells in culture and the transformation process or neoplastic processes that make stable cell lines immortal. Notable differences in placental development and function among racial groups highlight the need to address social determinants of health when studying early placental development and related pregnancy outcomes. Stem cell-derived models of in vitro trophoblast differentiation, including human embryonic stem cell (hESC)-- and induced pluripotent stem cell (iPSC)-technologies, may provide unique systems in which to reliably study the earliest events in normal and abnormal human placental development.
