The length of gestation is highly diverse among mammals. Equally diverse are the mechanisms initiating the timepoint of birth, even to the extent that this role is likely played by the maternal mechanisms in some mammals, and by the fetal mechanisms in others. Within species variation in gestational length can be lethal, both for the fetus (preterm birth) as well as for the mother (postterm birth). In humans, where the mechanism determining gestational length is unknown, preterm birth is one of the most common complications of pregnancy, even with the modern medicine involving between 5 and 12% of the pregnancies. Addressing this question with animal models is hindered by the evolutionary divergence among mammals in the reproductive traits and thus requires close attention to homology of single processes.

In this short talk, I will present work in progress on functional genetics of a locus, which has been associated in large GWAS study with the length of human gestation. So far, we have been able to localize the SNP in the human regulatory genome, determine the DNA mechanism, as well as the maternal uterine cell type in which this genetic change likely causes phenotypic effects. The uterine phenotype and gene expression in two gene-edited mouse lines further support the reasoning. Several open questions remain however, such as which developmental mechanisms are involved and how do the mechanisms in mouse translate to those determining gestational length in humans.