A “tug-of-war” between genes from mother and father appears to play a role in fetal development, according to a new study. File Photo by Khakimullin Aleksandr/Shutterstock
Dec. 27 (UPI) — The “battle of the sexes” starts in the womb, and it appears to play a role in fetal development, a study published Monday by the journal Developmental Cell found.
In experiments using mice, researchers at the University of Cambridge in England identified the signals sent by fetuses to control the supply of nutrients from the placenta, they said.
As fetuses develop, they communicate their increasing needs for food to receive nourishment via blood vessels in the placenta, the researchers said.
In the genetically engineered mice, they showed how the fetus produces a signal to encourage growth of blood vessels within the placenta.
This signal also causes modifications to other cells of the placenta to allow for more nutrients from the mother to go through to the fetus, creating a “tug-of-war” between genes inherited from the father and from the mother, according to the researchers.
“We’ve identified one way that the fetus uses to communicate with the placenta to prompt the correct expansion of these blood vessels,” study co-author Ionel Sandovici said in a press release.
“When this communication breaks down, the blood vessels don’t develop properly, and the baby will struggle to get all the food it needs,” said Sandovici, a post-doctoral researcher in metabolic diseases at the University of Cambridge’s Department of Obstetrics and Gynecology.
The fetus sends a signal in the form of a protein hormone called IGF2 that reaches the placenta through the umbilical cord, according to Sandovici and his colleagues.
In mice, the response to IGF2 in the blood vessels of the placenta is controlled by another protein, called IGF2R.
The two genes that produce IGF2 and IGF2R are “imprinted,” a process in which molecular switches on the genes identify their parental origin and can turn them on or off.
In the case of IGF2, only the copy of the gene inherited from the father is active, while only the copy of IGF2R inherited from the mother is active, according to the researchers.
“We’ve known for some time that IGF2 promotes the growth of the organs where it is produced,” Sandovici said.
“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,” he said.
The researchers used mice, as it is possible to manipulate their genes to mimic different developmental conditions, enabling them to study in detail the different mechanisms taking place.
In humans, levels of the protein in the umbilical cord progressively increase between 29 weeks of gestation and full term, or 39 to 40 weeks, the researchers said.
Excessive IGF2 is associated with too much growth, while a shortage of the protein is associated with too little growth, they said.
Babies that are too large or too small are more likely to suffer or even die at birth and they have a higher risk for developing diabetes and heart problems as adults.
The World Health Organization estimates that between 10% and 15% of babies grow poorly in the womb, often showing reduced growth of blood vessels in the placenta.
In humans, these blood vessels expand dramatically between mid and late gestation, reaching a total length of approximately 190 miles at full term Sandovici and his colleagues said.
The findings provide a better understanding of how the fetus, placenta and mother communicate with each other during pregnancy, they said.
This could lead to ways of measuring levels of IGF2 in the fetus and finding ways to use medication to normalize them to ensure healthy fetal growth, according to the researchers.
“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,” study co-author Miguel Constâncias said in a press release.
“There’s a tug-of-war taking place, a battle of the sexes at the level of the genome,” said Constâncias, a senior lecturer in reproductive biology at the University of Cambridge.