Foetuses use a copy of a gene inherited from their father to force their mother to release as much nutrients as possible during pregnancy, said UK scientists.
The unborn baby “remote controls” its mother’s metabolism so the two are in “a nutritional tug of war”, the researchers at the University of Cambridge have found.
The mother’s body wants the baby to survive but needs to keep enough glucose and fats circulating in her system for her own health, to be able to deliver the baby, breastfeed and to reproduce again.
The study published on Tuesday examines how the placenta communicates with the mother through the release of hormones so she will accommodate her baby’s growth.
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The placenta is a vital organ that develops with the foetus in pregnant women and other female mammals to support the developing foetus. In pregnant mice, scientists selectively altered the signalling cells in the placenta that tell mothers to allocate nutrients to her developing foetuses.
Co-author Prof Amanda Sferruzzi-Perri of St John’s College said: “It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the foetus.”
Dr Miguel Constancia, a co-author based at the Wellcome-MRC Institute of Metabolic Science, said: “The baby’s remote control system is operated by genes that can be switched on or off depending on whether they are a ‘dad’s’ or ‘mum’s’ gene’ – the so-called imprinted genes.
“Genes controlled by the father are ‘greedy’ and ‘selfish’ and will tend to manipulate maternal resources for the benefit of the foetuses, so to grow them big and fittest,” he said. “Although pregnancy is largely co-operative, 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 baby’s genes controlled by the father tend to promote foetal growth and those controlled by the mother tend to limit foetal growth, the study published in Cell Metabolism finds.
Prof Sferruzzi-Perri explained: “Those genes from the mother that limit foetal growth are thought to be a mother’s way of ensuring her survival, so she doesn’t have a baby that takes all the nutrients and is too big and challenging to birth. The mother also has a chance of having subsequent pregnancies potentially with different males in the future to pass on her genes more widely.”
Researchers deleted expression of an important gene called Igf2 in mice, which provides instructions for making a protein called ‘Insulin Like Growth Factor 2′. Similar to the hormone insulin, which is responsible for making and controlling glucose levels in our circulation, the gene promotes foetal growth and plays a key part in the development of foetal tissues including the placenta, liver and brain.
Dr Jorge Lopez-Tello, who contributed to the research, said: “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 foetus in insufficient amounts and the foetus doesn’t grow properly.”
Deleting Igf2 from the placenta’s signalling cells affects the production of other hormones that modulate the way the mother’s pancreas produces insulin, and how her liver and other metabolic organs respond, the scientists found.
Babies with Igf2 gene defects can be overgrown or growth-stunted. “Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signalling to the mother to allocate nutrients to the foetus,” Prof Sferruzzi-Perri said.
The mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life. “Our research highlights how important the controlled allocation of nutrients to the foetus is for the lifelong health of the offspring, and the direct role the placenta plays,” she said.
“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 foetal organs have developed and then how they’re going to function through life.”
The next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. This could lead to new strategies to target the placenta to improve health outcomes for mothers and babies.
