Solving the mystery of fetal size: the "gender war" begins in the womb

Scientists at the University of Cambridge discovered a key signal used by the fetus to control the nutritional supply of the placenta, revealing a tug-of-war between genes inherited from the father and mother
.

This study in mice can help explain why some babies are stunted in the womb

As the fetus grows, it needs to communicate its growing demand for food to the mother
.

It receives nourishment through the blood vessels in the placenta, which is a special organ that contains cells from babies and mothers

10% to 15% of infants are stunted in the uterus, usually as a result of decreased growth of blood vessels in the placenta
.

For humans, these blood vessels expand sharply between the second and third trimester of pregnancy, and the total length of the term is about 320 kilometers

In a study published today (December 27, 2021) in the journal Developmental Cell, a team led by scientists from the University of Cambridge used genetically engineered mice to show how the fetus generates a signal to promote The growth of blood vessels in the placenta
.

This signal will also change other cells in the placenta, allowing more nutrients from the mother to enter the fetus

The first author of the paper, Dr.
Ionel Sandovici, said: “When a fetus grows in the womb, it needs food from the mother.
The healthy blood vessels in the placenta are essential to help the fetus get the right amount of nutrients it needs.
Important
.

"

"We have identified a way for the fetus to communicate with the placenta to promote the proper expansion of these blood vessels
.

When this communication is interrupted, the blood vessels will not develop normally and the baby will have difficulty getting all the food they need

The research team found that the fetus sends a signal called IGF2 to reach the placenta through the umbilical cord
.

In humans, the level of IGF2 in the umbilical cord gradually increases between the 29th week of pregnancy and full term: too much IGF2 is associated with overgrowth, while insufficient IGF2 is associated with undergrowth

Dr.
Sandovici added: “We already know that IGF2 can promote the growth of the organs that produce it
.

In this study, we have shown that IGF2 is also like a traditional hormone-it is produced by the fetus, enters the fetal blood, and passes The umbilical cord and placenta work there

What is particularly interesting is that their findings reveal the fighting in the womb
.

In mice, the response to IGF2 in placental blood vessels is mediated by another protein called IGF2R
.

The two genes that produce IGF2 and IGF2R are "imprinted"-through this process, the molecular switch of the gene can recognize their parental origin, and can turn the gene on or off
.
In this case, only the IGF2 gene copy inherited from the father is active, and only the IGF2R gene copy inherited from the mother is active
.

Lead author Dr.
Miguel Constancia said: “One theory about imprinted genes is that the genes that fathers represent are greedy and selfish
.
They want to squeeze as much resources from their mothers as possible
.
But the genes expressed by the maternal line balance these Demand response
.
"

" In our research, the father’s genes drive the fetus’s need for larger blood vessels and more nutrients, while the mother’s placenta genes try to control how much nutrition she provides
.
This is a tug-of-war battle, a genomic level of gender.
War
.
"

The research team said their findings will enable people to better understand how the fetus, placenta, and mother communicate with each other during pregnancy
.
This in turn may lead to methods of measuring fetal IGF2 levels and finding ways to use drugs to normalize these levels or promote the normal development of the placental vasculature
.

The researchers used mice because it is possible to manipulate their genes to simulate different developmental conditions
.
This allows them to study in detail the different mechanisms that occur
.
The physiology and biology of mice have many similarities with humans, which allows researchers to simulate human pregnancy in order to better understand it
.

Reference: "The Imprinted Igf2-Igf2r Axis is Critical for Matching Placental Microvasculature Expansion to Fetal Growth" by Sandovici, I et al.
, 27 December 2021, Developmental Cell .

DOI: 10.
1016/j.
devcel.
2021.
12.
005