The Genomic Landscape of the Placenta: Mutations, Aneuploidy, Structural Variants and Why It Matters

Abstract

The placenta is an ephemeral yet vital organ supporting foetal development during pregnancy. About a third of pregnancies are complicated due to placental dysfunction. Despite its importance, the placenta has been, and still is, deeply understudied. Ethical challenges over access to developing human placentas and the lack of representative models, both animal and in vitro, have historically hindered progress in the field. However, recent advances in human in vitro models and other technologies are starting to reshape the field, providing new insights into placental biology. Recent research reveals the placenta as a genomically distinctive organ, exhibiting cancer-like features, such as a high mutation load, aneuploidy and genome amplification. These may underly its inherent properties, such as invasiveness and high proliferation, and unique dual role as both the exchange platform and barrier between mother and foetus. This literature review provides a comprehensive summary of the current knowledge on the genomic features of the human placenta and their potential functional impact. By identifying significant gaps in the current literature and suggesting new research directions, we highlight the need for a better understanding of placental genomics. Such understanding has the potential to inform diagnostic strategies and help the management of pregnancy complications, thereby improving maternal and neonatal outcomes.