Genetic conflict with fetus affects when women give birth

When it comes to the duration of pregnancy, the interests of the fetus and those carrying them may be slightly different. Now, the largest-ever study of how genes affect the timing of childbirth suggests that the two sides made an evolutionary compromise.

Gene variants that, in females, promote a shorter pregnancy also encourage faster fetal development when present in embryos. “They reached some kind of deal, the mother said: ‘I’m going to allow you to grow a little more, but I’m going to give up a little earlier’,” says Pol Sole Navas at the University of Gothenburg, Sweden.

Premature birth – defined as delivery before 37 weeks of pregnancy – is one of the leading causes of death among newborns globally, but the reasons are poorly understood.

To explore the genetic effects of pregnancy length, Sole Navais’ team pooled results from previous studies that included nearly 200,000 women who had started giving birth at different stages of pregnancy without being medically induced. Transgender people were not included.

These studies sequenced the DNA of both the women and their children, as well as noting aspects such as how long the pregnancy lasted and the birth weight of the babies.

Sole Navas’ team found 22 sites within the genome that each had a small effect on birthweight, with five that had the opposite effect when present in the mother or fetus. In other words, if a certain variant was present in the mother, it was associated with a shorter pregnancy, whereas if present in the fetus, it was associated with a longer pregnancy.

This supports the idea that the interests of the fetus and those carrying them conflict, because the longer the pregnancy, the larger the fetus usually grows, which makes the birth riskier for the mother, Sole Navas They say. Within limits, the fetus is more interested in getting bigger than the mother, he says.

But when fetal birth weight was considered, the picture became more complicated. When the effects of all gene variants were aggregated, those associated with shorter gestation were also linked to higher birth weight if inherited by the fetus.

If certain genetic variants in a fetus are associated with increased birth weight, the mother’s genome counters that using a single variant to reduce the length of pregnancy, says John Perry at Cambridge University. “The fetus is pushing in one direction and the mother is pushing in another.”

The team also found that some variants that affect how long a pregnancy lasts may also prevent labor from starting. previous studies It has been suggested in mice that the protein they encode may be involved in controlling uterine contractions.

Understanding more about how they have this contraction-regulating effect could lead to new drugs or to stop labor, says Sole Navas.