Nutrients diverted to fetus by gene inherited from father

Maternal metabolism is 'remote controlled' by the father's 'greedy' gene during pregnancy, according to new research by Cambridge scientists.

A copy of a gene inherited from the father, Igf2, has been discovered to send signals and force as many nutrients as possible from the mother to the fetus during pregnancy. The gene allows the fetus to 'remote control' the mother into giving them more nutrients.

'Genes controlled by the father are 'greedy' and 'selfish' and will tend to manipulate maternal resources for the benefit of the fetuses, so to grow them big and fittest.' said Dr Miguel Constância, co-senior author of the paper and associate professor in reproductive biology at the University of Cambridge. 'Although pregnancy is largely cooperative, there is a big arena for potential conflict between the mother and the baby, with imprinted genes and the placenta thought to play key roles.'

The genes inherited from the father promote the growth of the fetus by diverting nutrients from the mother to the baby. But genes from the mother tend to limit this. The limitation means the mother can then use these resources to deliver the baby, breastfeed and have more children. Additionally, it ensures the baby is not too large to birth. The gene imprinting leads to a nutritional tug of war between mother and fetus whereby she needs the glucose and fats to survive but also needs to provide nutrients for fetal growth and development.

Publishing their findings in Cell Metabolism, the researchers deleted Igf2 in the placenta of mice models to determine how the placenta communicates with the mother. The mice without Igf2 had lower levels of the gene's protein product, Igf2, leading to disrupted fetal growth.

'If the function of Igf2 from the father is switched off in signalling cells, the mother doesn't make enough amounts of glucose and lipids – fats – available in her circulation... These nutrients, therefore, reach the fetus in insufficient amounts and the fetus doesn't grow properly.' added Dr Jorge Lopez-Tello, a lead author of the study and Sir Henry Wellcome postdoctoral fellow at the University of Cambridge.

The Igf2 gene promotes fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain. Babies born with a defective Igf2 gene can have stunted growth or be overgrown. The study showed that deleting Igf2 from the placenta's signalling cells resulted in smaller mice at birth that showed early signs of obesity and diabetes in later life.

'Our research highlights how important the controlled allocation of nutrients to the fetus is for the lifelong health of the offspring, and the direct role the placenta plays.' added Professor Amanda Sferruzzi-Perri, co-senior author and professor in fetal and placental physiology at the University of Cambridge. 'The placenta is an amazing organ. At the end of pregnancy, the placenta is delivered by the mother, but the memories of how the placenta was functioning leaves a lasting legacy on the way those fetal organs have developed and then how they're going to function through life.'

The scientists aim to research how the gene controls placental hormones, and also to investigate whether there are any potential changes to the germline that may affect future generations.