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Centre for Trophoblast Research


Research led by scientists from the Constância Group has identified a key signal that a fetus uses to control its supply of nutrients from the placenta. The way that a fetus grows ‘in sync’ with the placenta was not known until now.

The study, carried out in mice as a 'model' (proxy) for human pregnancy, could help explain why some babies grow poorly in the womb.

In nearly all mammals, the fetus receives nourishment via blood vessels in the placenta, a temporary, specialised organ thought to have evolved between 150 and 200 million years ago. The placenta contains cells from both baby and mother and acts as the interface between them, allowing exchange of molecular signals, nutrients and more. The placenta is continuously bombarded by signals from both 'sides' and needs to integrate and process these signals to ensure healthy development. As it grows, the fetus must access more nutrients and one of the ways this can happen is by promoting the growth of a bigger and better blood vessel network in the placenta; in humans, placental blood vessels reach a total length of approximately 320 kilometres at term. Not much has been known about how the fetus communicates this increasing need for food to the mother. Between 10% and 15% of babies grow poorly in the womb and reduced growth of blood vessels in the placenta is often seen in these cases.

The study, published in Developmental Cell, used genetically engineered mice to show how the fetus produces a signal to encourage growth of blood vessels within the placenta. The signal, known as IGF2 (insulin like growth factor 2), reaches the placenta through the umbilical cord. In humans, levels of IGF2 in the umbilical cord progressively increase between 29 weeks of gestation and term: too much IGF2 is associated with too much growth, while not enough IGF2 is associated with too little growth. Babies that are too large or too small are more likely suffer or even die at birth, and have a higher risk of developing diabetes and heart problems as adults.

As the placental vasculature develops, a reservoir of IGF2 also forms there, as this is produced continuously in the cells that line the expanding blood vessels. The pool of IGF2 influences other types of cells in the placenta to comply with the nutrient demands of the fetus.


Ionel Sandovici, Aikaterini Georgopoulou, Vicente Pérez-García, Antonia Hufnagel, Jorge López-Tello, Brian Y.H. Lam, Samira N. Schiefer, Chelsea Gaudreau, Fátima Santos, Katharina Hoelle, Giles S.H. Yeo, Keith Burling, Moritz Reiterer, Abigail L. Fowden, Graham J. Burton, Cristina M. Branco, Amanda N. Sferruzzi-Perri, Miguel Constancia.

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