Complete path of placental development mapped

Cambridge researchers have mapped out a detailed trajectory of human placental development and described its interaction with the maternal uterus.

The findings, published in Nature, could improve understanding of pregnancy-related disorders such as unexplained stillbirths and pre-eclampsia, which affects around six percent of UK pregnancies, and globally causes around 50,000 maternal deaths a year.

'For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps,' said co-first author, Anna Arutyunyan, a PhD student from the Wellcome Sanger Institute and the University of Cambridge. 'This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide.'

Previous studies of human placental development have been limited by the lack of available samples. This research used a rare collection of first-trimester pregnant human uteruses, collected over 30 years ago and stored in liquid nitrogen.

'This research is unique as it was possible to use rare historical samples that encompassed all the stages of placentation occurring deep inside the uterus,' said study senior co-author, Professor Ashley Moffett, professor of reproductive immunology from the University of Cambridge.

Together with scientists from Germany and Switzerland, they studied the transcriptomic and epigenetic activity seen at implantation sites (where embryos attach to the endometrium of the uterus, leading to placental formation). As different cell types have different transcriptomic and epigenetic profiles, this allowed the researchers to establish which cell types were involved in placental development.

Using computational techniques, they then explored cellular interactions between placental and maternal cells. Specifically, they studied the influence of placental cells on the transformation of maternal uterine blood vessels, identifying proteins and receptors involved in this process.

The outermost layer of the developing placenta is formed of cells called trophoblasts. These cells infiltrate the uterus, transforming maternal blood vessels to allow passage of oxygen and nutrients to the fetus. Abnormalities in this process are linked to common pregnancy disorders such as pre-eclampsia.

The authors hope their findings could be used to develop experimental models to better understand pregnancy-related disorders, and have made their data freely available as part of the Human Cell Atlas programme.

'We are glad to have created this open-access cell atlas to ensure that the scientific community can use our research to inform future studies,' said Professor Moffett.