The curious case of the placental genome

The human placenta is among the few, if not the only, healthy mammalian tissues that may exploit a cancer-like somatic genome for its function. Acting simultaneously as the lungs, kidneys, liver and gastrointestinal tract, the placenta mediates nutrient and gas exchange, blocks out toxins and pathogens, removes fetal waste, and secretes hormones essential for pregnancy. Recent research has revealed that the placenta is a genomically distinctive organ with an unusually high mutational load, abundant structural variations, prevalent aneuploidy and genome amplification, as well as a tissue-sized multinucleated syncytium. These features may underlie its invasiveness and high levels of cell proliferation, as well as its dual role as both exchange platform and barrier between mother and fetus. Here, we review our current understanding of the unique genomic features of the human placenta and their potential functions. We identify prevalent gaps in current literature and suggest new research directions to address the need for a better understanding of placental genomics. Such understanding has the potential to inform clinical diagnostic and management strategies for pregnancy complications, thereby improving pregnancy outcomes.