Cell atlas of placenta and uterus published

Fetal cells invade the uterine lining without triggering the maternal immune system, a new cell atlas has shown.

The research uncovers highly complex interactions between fetal cells from early embryonic development and the mother's immune system during placenta formation. These help explain how these genetically-unmatched cells do not trigger an immune reaction, as well as how uterine arteries are remodelled to provide adequate blood supply.

'When I first read about it, I thought, "This is so bizarre"', said Dr Michael Angelo, who led the research at Stanford University in California. 'There is nothing else like this in human biology.'

In the first trimester of pregnancy, fetal cells called EVTs invade the uterus lining, where they play a crucial role in modifying the arteries that will supply the fetus with oxygen and nutrients throughout the pregnancy.

These blood vessels need to become large and dilated to allow plenty of slow blood flow, allowing the exchange of nutrients and waste products with the fetal blood in the placenta. It is thought that if this does not happen sufficiently, the mother's blood pressure can rise to compensate, contributing to the development of preeclampsia.

The study, published in Nature, used placental tissue samples donated by 66 women to map the activity of EVTs and maternal immune cells within placental tissue between six and 20 weeks gestation.

The researchers are also trying to understand how the mother's immune system knows not to attack the EVT cells. Normally, any foreign cells would be targeted and destroyed by the immune system, but they found that the immune reaction decreased as the pregnancy progressed.

The researchers suggest that when this immune response does not calm down enough, this could result in miscarriage, or later pre-eclampsia.

'Maternal-fetal tolerance around month two or three of pregnancy is critical for getting past the first trimester,' said Dr Angelo. 'It would be ideal if we could identify ahead of time who was at risk and give some sort of preparation for the immune system before pregnancy.'

This study is part of the wider Human Biomolecular Atlas Program (HuBMAP) which aims to 'create an open, global atlas of the human body at the cellular level' to aid understanding of how human cell location and gene activity affect tissue function and health.

'In research, we have a habit of studying things that are abnormal without really understanding what normal looks like,' said Dr Angelo.