‘Battle of the sexes’ starts in the womb as male and female genes fight over nutrition

CAMBRIDGE, Mass. — The battle of the sexes starts in the womb, as the father and mother’s genes fight over nutrition, according to a new study. Researchers from the University of Cambridge discovered that as a fetus grows, a genetic tug-of-war takes place to gather as many nutrients as possible from the placenta.

Since their biology is similar to human genetic makeup, the researchers decided to carry out the study on mice to help explain why some babies struggle to grow properly in the womb. As babies grow, they need a way to communicate how hungry they are to their mother.

The fetus receives its nourishment via blood vessels in the placenta, which is a special organ containing cells from both the baby and its mother. Between 10 percent and 15 percent of babies grow poorly in the womb and they often show reduced growth of blood vessels in the placenta. While a human baby is growing, these blood vessels expand dramatically between mid and late pregnancy.

Perfect communication is essential during pregnancy

Image showing sections of the fetus and placenta.
Image showing sections of the fetus and placenta. A team of Cambridge scientists discovered as a foetus grows, a genetic tug-of-war between the father and mother’s genes takes place to get as many nutrients as possible from the placenta. Because their biology is similar to our genetic makeup, the researchers decided to carry out the study on mice to help explain why some babies struggle to grow properly in the womb. As babies grow, they need a way to communicate how hungry they are to their mum.

During the study, the researchers found that the signal also causes changes to other cells of the placenta to allow more nutrients from the mother’s body to go through to the fetus.

“As it grows in the womb, the fetus needs food from its mum, and healthy blood vessels in the placenta are essential to help it get the correct amount of nutrients it needs,” says study first author Dr. Ionel Sandovici in a university release.

“We’ve identified one way that the fetus uses to communicate with the placenta to prompt the correct expansion of these blood vessels. When this communication breaks down, the blood vessels don’t develop properly and the baby will struggle to get all the food it needs.”

The experts found that the fetus sends a signal known as “IGF2,” that reaches the placenta through the umbilical cord. In human babies, the levels of IGF2 in the umbilical cord increase between the 29th week of pregnancy and their due date. However, producing the right amount of IGF2 is a balancing act for the baby.

Too much IGF2 can lead to too much growth, while not enough IGF2 results in too little growth. For the babies that are too large or too small, they are more likely to suffer or even die at birth. If they do survive, they have a higher risk of developing diabetes and heart problems as adults.

“We’ve known for some time that IGF2 promotes the growth of the organs where it is produced. In this study, we’ve shown that IGF2 also acts like a classical hormone – it’s produced by the fetus, goes into the fetal blood, through the umbilical cord and to the placenta, where it acts,” Dr. Sandovici adds.

Genes can be ‘greedy and selfish’

Their study’s findings revealed an interesting discovery about the tussle that takes place in the womb. Dr. Sandovici says that in the mice babies, the response to IGF2 in the blood vessels of the placenta is managed by another protein called IGF2R. He adds that the two genes that produce both IGF2 and IGF2R are “imprinted.”

This occurs in all people when they inherit two copies of genes, one from their mother and one from their father. Usually, both copies of these genes are active or “switched on” but in some cases, only one of the two copies is turned on. Which copy is active, depends on the parent of origin.

In this case, researchers found that only the copy of IGF2 which was inherited from the father was active, while only the copy of IGF2R from the mother was active.

“One theory about imprinted genes is that paternally-expressed genes are greedy and selfish. They want to extract the most resources as possible from the mother. But maternally-expressed genes act as countermeasures to balance these demands,” lead study author Dr. Miguel Constância explains.

“In our study, the father’s gene drives the fetus’s demands for larger blood vessels and more nutrients, while the mother’s gene in the placenta tries to control how much nourishment she provides. There’s a tug-of-war taking place, a battle of the sexes at the level of the genome.”

The team believes that their findings will help people understand how the fetus, placenta, and the mother communicate with each other during pregnancy. This could then lead to ways of measuring the levels of IGF2 in the fetus and finding ways to use medication to normalize these levels and to promote the healthy development of the vital placental vasculature organ.

The study’s findings are published in the journal Developmental Cell.

South West News Service writer Georgia Lambert contributed to this report.

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