Organoids used to investigate placenta infections

Placenta organoids created from cultured human placenta cells have been used to shed light on several types of infection in early pregnancy.

Researchers created a cell map of infected placenta organoids to investigate immune reactions in the placenta to different infections, and the impact it might have on the developing fetus. Pregnant women are advised to avoid certain foods to avoid infections that can lead to pregnancy complications caused by toxoplasmosis, a parasitic infection, and listeria, which is a bacteria. Infection with the parasite that causes malaria in humans was also investigated. They found all caused inflammation and infection-specific reactions. 

'Infections during pregnancy can have devastating impacts, and there are limited pregnancy-specific treatment options that can help,' said Dr Roser Vento-Tormo group leader at the Wellcome Sanger Institute, near Cambridge, and co-senior author of the paper published in Cell Systems.

'By mapping the pathways involved in infection during early-stage pregnancy in single-cell resolution, and developing new placental models to study this, we hope that our research can be used by the research community worldwide to help develop new ways to understand and treat pregnancy complications that impact millions of lives every year.'

Infections during pregnancy can lead to miscarriage and stillbirth, developmental conditions and low birth weight in babies born after infection. They can also lead to maternal death, sepsis, and pregnancy complications.

Researchers from the Wellcome Sanger Institute and the University of Cambridge used cells taken from human placentas at five to 14 weeks post-conception to create placenta organoids for their investigations. They then created a cell map of the organoids.

Hofbauer cells, a type of fetal immune cell, were found to be activated in different pathways in each different type of infection. This was the first time that these immune cells have been shown to play a role in the immune defences of the placenta, authors said.

Malaria infection was found to adapt to the microenvironment of the placenta and influence nutrient uptake of cells, and authors have proposed that toxoplasmosis could infect the fetus via infection of fetal immune cells in the placenta, which travel into the fetus. 

Authors propose that dysregulation of homeostasis in the placenta could lead to some of the complications seen in pregnant women with these infections, and propose that the inflammatory response in the placenta could be a future treatment target. 

'While infections during pregnancy have been known to cause complications, including miscarriage and stillbirth, very little has been known about the underlying mechanisms,' said Dr Regina Hoo a post-doctoral researcher at the Wellcome Sanger Institute, and co-first author of the study.

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