A new study has demonstrated how a gene called HAND2 can play a role in the timing of labour.
The timing of labour
The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to processes that subsequently result in disease. The nature of maternal-foetal interactions, how they develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Gene expression changes at the maternal-foetal interfaces underlie evolutionary differences in pregnancy. These differences are likely to also influence pathologies of pregnancy.
Understanding the mechanistic origin of pregnancy and how it diverged may provide unique insights into the origins of pregnancy disorders. We currently don’t fully understand why humans go into labour. In many animals, as gestation progresses, the level of progesterone increases until a few hours before birth where it drops. But in humans, this does not happen – progesterone levels do not drop off.
The evolution of HAND2
In this study, published in eLife, researchers used several datasets to study genes that were active in the uterine linings of different animals while pregnant or carrying eggs. These animals included placental mammals and marsupials as well as egg-laying species like platypuses, birds, lizards and frogs.
Their analyses revealed that the transcription factor, HAND2, evolved to be turned on in the uterine linings of placental mammals during pregnancy. This was not present in the other studied species. This transcription factor suppresses oestrogen signalling thereby allowing blastocyst implantation. The team found that HAND2 was dynamically expressed throughout the menstrual cycle and pregnancy, gradually declining as labour neared. This protein specifically regulates a small but distinct set of target genes in endometrial stromal fibroblasts. Interestingly, the team found that the HAND2 promoter loops to a distal enhancer. The team found that this enhancer contains SNPs that are implicated in the regulation of gestation length and birth weight.
Collectively, these results connect HAND2 expression with the evolution of implantation and gestation length regulation. The team note that utilising organoid models of the human maternal-foetal interface will allow for future in vitro 3D manipulation which will be instrumental in studying human pregnancy.
Image credit: By Aleksandra Nigmatulina – canva.com