Human placenta map offers hope against pregnancy threats

Using ‘mini placenta’ models, researchers from the Wellcome Sanger Institute, the University of Cambridge, the University of Dundee, together with other collaborators were able to identify responses to early infections.

Their work was outlines in Cell Systems journal with a focus on the above diseases, each of which can cause complications and miscarriage. 

Among the findings, the work revealed that placental immune cells probably act as defences against pathogens and that pregnancy complications may result from secondary inflammation during infection periods.

While the placenta can enable the passage of nutrients while simultaneously obstructing pathogens and toxins those derive from toxoplasmosis and listeria can traverse the placenta; malaria parasites can attach to the exterior.

Using ex vivo models from human placenta samples offered a far more detailed and accurate picture of infection responses, mapped to single cell resolution level. The research team identified a Hofbauer foetal immune cell activated in response to all three of the diseases studied, but operating in different pathways. This marked the first time, they stated, that the defensive role of immune cells in the placenta against pathogens had been demonstrated.

However, the studies also revealed that some pathogens, notably the toxoplasmosis parasite T. gondi, can infiltrate immune cells to avoid the defence response as well as travel around the host.

Co-first author, the Wellcome Sanger Institute’s Dr Regina Hoo, said: “While infections during pregnancy have been known to cause complications, very little has been known about the underlying mechanisms.

“Our research shows that even with pathogens that cannot cross the placenta, the secondary inflammation from the immune system may be responsible for disrupting foetal development. Identifying key processes involved with the inflammation pathway could help us develop pregnancy-specific treatments that minimise this in the future.” 

The placental study forms part of the Human Cell Atlas consortium,  whose goal is to map every cell type in the human body to transform understanding of health and disease. 

Elias Ruiz-Morales, also a co-first author from the Wellcome Sanger Institute, said: “We discovered that placental immune cells called macrophages can protect the placenta against infections. 

“This is the first time that placental immune cells have been shown to play a defensive role in early-stage pregnancy in humans, and that these immune cells can be hijacked by toxoplasma during infection. Understanding more about how the placental immune system works can help give new insights into pregnancy complications.”