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How is human pregnancy unique?

In a recent study, researchers delved into the evolutionary history of pregnancy, identifying hundreds of genes that evolved to be switched on or off in humans during early pregnancy.

Evolution of pregnancy

Evolutionary changes in the early development of anatomical systems are key for their functional conservation and transformation into various tissue and organ systems with new physiological functions. These same evolutionary and developmental constraints have restricted the range of genetic and environmental perturbations that can occur before dysfunction and disease. The evolution of the structures and functions within the female reproductive system and extra-embryo foetal membrane ultimately underlie the evolution of pregnancy. As a result, understanding the evolutionary and developmental history of the cells, tissues and organs involved in pregnancy may help determine the molecular aetiology of adverse pregnancy outcomes. Such outcomes include infertility, recurrent spontaneous abortion, preeclampsia and preterm birth.

The evolution and diversification of pregnancy across extant mammals ranges across major stages, including matrotrophy, placentation and viviparity. There are also considerable variations in pregnancy traits among eutherians (or ‘placental’ mammals). Humans, for example, have evolved interstitial trophoblast invasion, shorter interbirth intervals and longer pregnancy and labour than other primates. In addition, humans are also more susceptible to pregnancy complications than other primates.

Gene expression changes during pregnancy

In a recent study, published in eLife, researchers used comparative transcriptomics to reconstruct the evolutionary history of gene expression changes in the human endometrium during pregnancy. The researchers compared gene activity of the human endometrium to other animals during pregnancy or while carrying eggs, including lizards and marsupials. They also aimed to identify genes that were gained (recruiter genes) or lost in the primate and human lineages.

The team showed that gene expression changes in the human endometrium during pregnancy were associated with the evolution of human-specific traits and pathologies of pregnancy. They specifically identified genes enriched for immune functions and diseases, such as preterm birth and preeclampsia, as well as other pathways not previously implicated in pregnancy.

The researchers further explored the function of three recruiter genes which implicated them in a novel signalling system at the maternal-foetal interface (HTR2B), maternal-foetal immunotolerance (PDCD1LG2) and remodelling of uterine spiral arteries and deep placental invasion (CORIN). These functions are important to the health of a pregnancy.

Intriguingly, the team also discovered that the recruited genes were enriched in a serotonin signalling pathway. This finding is exciting as it suggests that some of these genes may be involved in communicating with the brain during pregnancy.

Implications for human pregnancy

In summary, this study has identified a suite of genes that are suspected to contribute to cell-to-cell communication, regulation of the immune response and inflammation, and the ability of the human placenta to burrow deeply into the uterine wall.  

The data from this study highlights the value of evolutionary medicine. It also lays the foundation for future studies that aim to understand, prevent and treat adverse pregnancy outcomes.

Study Lead, Mirna Marinić, expressed:

“Our paper really highlights the useful role of evolutionary techniques in translational research.

The three genes we identified (HTR2B, PDCD1LG2 and CORIN) will advance work on signalling systems at the crucial maternal-foetal interface, which impacts the success and health of a pregnancy.”

Image credit: canva


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Endometrium / Fertility / Pregnancy