Scientists from the University of Cambridge have made a fascinating discovery about the intricate relationship between unborn babies and their mothers during pregnancy.

According to their recent study, fetuses employ a gene inherited from their fathers to compel their mothers to provide them with additional nutrients.

This mechanism effectively allows the unborn baby to “remote-control” the mother’s metabolism, resulting in a delicate nutritional struggle between the two. While the mother’s body naturally aims to ensure the baby’s survival, it must also maintain adequate glucose and fat levels for her own well-being, childbirth, breastfeeding, and potential future reproductive endeavors.

The research, conducted by the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, sheds light on how the placenta communicates with the mother by releasing hormones that encourage her to support the baby’s growth.

The placenta, a crucial organ that develops alongside the fetus in pregnant women and other female mammals, plays a vital role in facilitating the fetus’s development. To investigate this process, scientists selectively modified the signaling cells in the placenta of pregnant mice, which regulate the allocation of nutrients from the mother to her developing fetuses.

Professor Amanda Sferruzzi-Perri, a leading authority in Fetal and Placental Physiology and a co-senior author of the study, emphasized the significance of their findings: this is “the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus.”

Dr. Miguel Constancia, an MRC Investigator affiliated with the Wellcome-MRC Institute of Metabolic Science and a co-senior author of the study, explained that the “remote control” system employed by the baby is regulated by specific genes, which can be activated or deactivated based on whether they are inherited from the mother or father. These imprinted genes, as they are known, controlled by the father, are characterized as “greedy” and “selfish” since they tend to manipulate the mother’s resources to maximize the fitness and growth of the fetuses. Although pregnancy is predominantly cooperative, the presence of imprinted genes and the placenta creates an arena for potential conflict between the mother and the baby.

The study, published in Cell Metabolism, demonstrates that genes inherited from the father promote fetal growth, while those inherited from the mother tend to restrict it. Professor Sferruzzi-Perri explained that the mother’s genes limiting fetal growth serve as a safeguard for her own survival, ensuring that she does not give birth to an overly large and challenging baby that would consume all available nutrients. Moreover, this allows the mother to have subsequent pregnancies with different fathers, facilitating the wider dissemination of her genes.

By deleting a critical imprinted gene called Igf2, responsible for producing a protein called “Insulin Like Growth Factor 2,” the researchers observed the impact on fetal growth. This gene, analogous to insulin, plays a crucial role in the development of fetal tissues, including the placenta, liver, and brain, while also promoting fetal growth. When the expression of Igf2 was silenced in the placenta’s signaling cells, the mother’s circulation did not contain sufficient glucose and fats, thus depriving the fetus of adequate nutrients and hindering its proper growth.

Furthermore, they discovered that removing Igf2 from the placenta’s signaling cells affected the production of other hormones responsible for regulating the mother’s insulin sensitivity, as well as the responses of her liver and other metabolic organs. According to Professor Sferruzzi-Perri, this finding indicates that Igf2 controls the hormones that reduce insulin sensitivity in the mother during pregnancy, thereby ensuring that glucose is readily available in circulation for transfer to the fetus.

The study revealed that mice lacking the Igf2 gene had smaller offspring at birth, and these offspring exhibited early signs of diabetes and obesity later in life.

Professor Sferruzzi-Perri added:

“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.”

Moving forward, the researchers aim to unravel the precise mechanisms through which Igf2 influences placental hormones and their specific functions. This ongoing research could potentially lead to the discovery of new strategies that target the placenta to enhance health outcomes for both mothers and babies.

Source: 10.1016/j.cmet.2023.06.007

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