Study finds, 'greedy' genes from father encourage unborn babies to steal their mother’s food

These exciting findings shed light on how the genes inherited from the father in the placenta (a temporary organ that develops inside the females during pregnancy to nourish their fetus) remote-control a mother’s metabolism. 

The greedy gene mechanism

While greedy genes promote fetal growth, the genes from the mother keep a check on them by allocating nutrients to the fetus in a limited manner. To understand the significance of this mechanism in detail, the researchers performed an interesting experiment.

They deleted a gene named Igf2 from the placenta of pregnant mice. This gene ensures proper growth and development of fetal tissues. 

The absence of Igf2 expression negatively affected the release of insulin-like growth factor 2 protein, which is responsible for glucose production. Plus, it also affected the hormones that controlled the release of insulin from the pancreas and influenced liver activity. This one gene in the placenta had the power to change the mother’s metabolism.

“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,” said Dr. Jorge Lopez-Tello, lead study author. 

The researchers claim that deficiency of the Igf2 gene could lead to overgrown or undergrown babies. The mice born to mothers with placentas lacking the Igf2 gene showed symptoms of diabetes, and as they grew, they became obese.

These results highlight that Igf2 plays a vital role in allocating nutrients from mother to fetus, and this allocation mechanism plays a crucial role in ensuring the optimal health of the offspring.

The UC team will continue their research. They are currently studying how Igf2 influences placental hormones and how changing the chemistry of these hormones could benefit the health of mothers and fetuses.

The study is published in the journal Cell Metabolism.

Study Abstract:

Maternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology to enhance placental nutrient transfer, but the mechanisms involved remain unclear. The imprinted Igf2 gene is highly expressed in murine placental endocrine cells. Here, we show that Igf2 deletion in these cells impairs placental endocrine signaling to the mother, without affecting placental morphology. Igf2 controls placental hormone production, including prolactins, and is crucial to establish pregnancy-related insulin resistance and to partition nutrients to the fetus. Consequently, fetuses lacking placental endocrine Igf2 are growth-restricted and hypoglycaemic. Mechanistically, Igf2 controls protein synthesis and cellular energy homeostasis, actions dependent on the placental endocrine cell-type. Igf2 loss also has additional long-lasting effects on offspring metabolism in adulthood. Our study provides compelling evidence for an intrinsic fetal manipulation system operating in the placenta that modifies maternal metabolism and fetal resource allocation, with long-term consequences for offspring metabolic health.