Unborn Babies Use Genes From Dad to “Remote-Control” Mothers for Extra Food
This “remote control” system involves hormonal signals from the placenta, which ensure the fetus grows optimally by altering the mother’s metabolic processes. Remarkably, this battle for nutrients is a delicate balance, crucial not just for fetal growth but also for the mother’s health and her future reproductive potential.
Nutritional Control in Pregnancy
Cambridge scientists have discovered that fetuses use a gene inherited from their father to influence their mother’s body into providing more nutrients during pregnancy.This creates a kind of “nutritional tug of war,” where the unborn baby ‘remote controls’ its mother’s metabolism to maximize its growth, while the mother’s body balances her own need to maintain health. The mother must ensure enough glucose and fats remain available for her energy needs, to sustain the pregnancy, support breastfeeding, and allow for future pregnancies.
Hormonal Signaling by the Placenta
A University of Cambridge study explored how the placenta plays a key role in this process. By releasing specific hormones, the placenta communicates with the mother’s body to prioritize the baby’s growth. This vital organ, which develops alongside the fetus, supports fetal development in humans and other mammals. In experiments with pregnant mice, scientists modified the signaling cells in the placenta that regulate how nutrients are allocated to the fetus.Professor Amanda Sferruzzi-Perri, Professor in Fetal and Placental Physiology, a Fellow of St John’s College and co-senior author of the paper, said: “It’s the first direct evidence that a gene inherited from the father is signaling to the mother to divert nutrients to the fetus.”
Gene Wars: Maternal vs Paternal Influences
Dr. Miguel Constancia, MRC Investigator based at the Wellcome-MRC Institute of Metabolic Science and co-senior author of the paper, 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 fetuses, so to grow them big and fittest. 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 findings by researchers from the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science, have been published in Cell Metabolism.
The baby’s genes controlled by the father tend to promote fetal growth and those controlled by the mother tend to limit fetal growth.
Professor Sferruzzi-Perri explained: “Those genes from the mother that limit fetal 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.”
Genetic Manipulation and Nutrient Allocation
Researchers deleted the expression of an important imprinted gene called Igf2, 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 fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain.Dr. Jorge Lopez-Tello, a lead author of the study based at the University’s Department of Physiology, Development and Neuroscience, said: “If the function of Igf2 from the father is switched off in signaling 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.”
The scientists found that deleting Igf2 from the placenta’s signaling 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.
“We found Igf2 controls the hormones responsible for reducing insulin sensitivity in the mother during pregnancy. It means the mother’s tissues don’t absorb glucose so nutrients are more available in the circulation to be transferred to the fetus,” said Professor Sferruzzi-Perri.
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 signaling to the mother to allocate nutrients to the fetus,” added Professor Sferruzzi-Perri.
The mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life.
Professor Sferruzzi-Perri said: “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.
“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 next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. Future research could help scientists discover new strategies to target the placenta to improve health outcomes for mums and babies.
embryonic development, fetal genetics, gene expression, DNA signaling, prenatal growth, genetic markers, cellular differentiation, genomic regulation, epigenetics, maternal inheritance, developmental biology, CRISPR technology, hereditary traits, organogenesis, genomic imprinting, fetal adaptation, molecular pathways, neurogenesis, gene editing, placental biology.
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