Health during pregnancy and beyond: Fetal trophoblast cells as chief co-ordinators of intrauterine growth and reproductive success.

Abstract Differentiation of extra-embryonic tissues and organs, notably the placenta, is vital for embryonic development and growth throughout gestation, starting from a few days after fertilization when the trophoblast cell lineage arises until parturition. In utero metabolic programming events may even extend the impact of placental function well into adulthood as they may predispose the offspring to common pathologies such as diabetes and cardiovascular disease. This review summarizes key steps that lead up to formation of a functional placenta. It highlights recent insights that have advanced our view of how early trophoblast expansion is achieved and how sufficient maternal blood supply to the developing fetus is secured. Exciting cumulative data have revealed the importance of a close cross-talk between the embryo proper and extra-embryonic trophoblast cells that involves extracellular matrix components in the establishment of a stem cell-like niche and proliferation compartment. Remarkably, placental function also relies on beneficial interactions between trophoblast cells and maternal immune cells at the implantation site. Our growing knowledge of the molecular mechanisms involved in trophoblast differentiation and function will help to devise informed approaches aimed at deciphering how placentation is controlled in humans as an essential process for reproductive success and long-term health.