Genetic conflict with the fetus influences when women give birth

When it comes to pregnancy duration, fetuses and those carrying them may have slightly different interests. Now the biggest study into how genes affect the timing of childbirth suggests that both parties have reached a evolutionary compromise.

Embarrassed variants which, in women, promote shortening pregnancy, also encourage faster fetal growth when present in fetuses. “They made a sort of deal, with the mum saying, ‘I’m going to let you grow a little taller, but I’m going to give birth a little earlier,'” says Pol Solé Navais at the University of Gothenburg, Sweden.

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

To explore the genetic influences of pregnancy duration, Solé Navais’ team pooled the results of previous studies that together included around 200,000 women who went into labor at different stages of pregnancy without having been medically induced. Transgender people were not included.

These studies sequenced the DNA of women and their babies, as well as aspects such as the duration of pregnancies and the weight of babies at birth.

Solé Navais’ team found 22 sites in the genome that each had a small influence on the timing of birth, five of which had opposite effects 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, while if it was present in the fetus, it was associated with a longer pregnancy.

This supports the idea that fetuses and those who carry them have opposing interests, because the longer a pregnancy lasts, the larger a fetus typically grows, making the birth riskier for the mother, says Solé Navais. Within certain limits, the fetus therefore has a greater interest in growing than the mother, he says.

But when the birth weight of the fetus was taken into account, the picture became more complicated. When the effects of all genetic variants were aggregated, those related to shorter pregnancy were also related to higher birth weight if inherited by the fetus.

If certain genetic variants in the fetus are associated with increased birth weight, the mother’s genome counteracts this by using the same variants to reduce pregnancy duration, says John Perry at the University of Cambridge. “The fetus pushes one way and the mother pushes the other way.”

The team also found that some of the variants that influence how long a pregnancy lasts can also prevent labor from starting. Previous studies in rats suggest that the proteins they encode may be involved in regulating uterine contractions.

Better understanding how they have this contraction-regulating effect could lead to new drugs that trigger or prevent labor, explains Solé Navais.