HSE scientists uncover mechanism behind placental lipid metabolism disorders in preeclampsia

Scientists at HSE University have discovered that in preeclampsia—one of the most severe complications of pregnancy—the placenta remodels its lipid metabolism, reducing its own cholesterol synthesis while increasing cholesterol transfer to the foetus. This compensatory mechanism helps sustain foetal nutrition but accelerates placental deterioration and may lead to preterm birth. The study findings have been published in Frontiers in Molecular Biosciences.

Preeclampsia affects up to 8% of pregnancies worldwide and is one of the leading causes of maternal and perinatal mortality. The condition is characterised by impaired blood flow to the placenta, hypoxia, and alterations in lipid metabolism. 

Despite the prevalence of preeclampsia, its molecular mechanisms remain poorly understood. Biologists at HSE University analysed alterations in lipid metabolism associated with this condition. They used single-cell RNA sequencing data from placental tissue in complicated pregnancies, as well as a placenta-on-a-chip cell model with induced hypoxia. This approach made it possible to compare gene expression changes across different subtypes of trophoblast cells—specialised placental cells that supply nutrients to the foetus and ensure its implantation into the uterine wall.   

The analysis showed that preeclampsia is associated with pronounced remodelling of lipid metabolism, with the nature of these changes depending on the trophoblast cell type. The scientists observed reduced activity of pathways responsible for cholesterol synthesis and uptake from the bloodstream, while at the same time noting an increase in the transfer of nutrients from the mother to the foetus. 

Comparison of the sequencing data with the on-chip cell model confirmed the key role of hypoxia in triggering changes associated with preeclampsia and made it possible to identify potential molecular regulators of this process—the PCSK9 and SNX17 genes.

'In preeclampsia, placental cells sacrifice their own cholesterol needs and shift toward transferring lipids to the foetus in order to preserve foetal development and compensate for nutritional deficiencies. As a result, the placenta ages and deteriorates more rapidly due to insufficient access to essential nutrients, which can lead to preterm birth,' explains Evgeny Knyazev, Head of the HSE Laboratory of Molecular Physiology and author of the article.

The results provide a new perspective on the mechanisms by which the placenta adapts to oxygen deficiency and suggest that the observed remodelling of lipid metabolism serves as a compensatory mechanism to maintain lipid supply to the foetus under conditions of limited resources.

'To effectively treat a disease, it is essential to understand its nature—to determine what is happening in the body and which mechanisms are at play. That is why basic research is so important,' says Evgeny Knyazev. 'We have identified specific genes involved in the regulation of lipid metabolism and found that many of the observed disorders are associated with impaired cholesterol uptake from the blood. It is possible that existing cholesterol-regulating medications could help the maternal body adapt to the changes that occur in preeclampsia.' 

Evgeny Knyazev received an award in the Biology category of the Moscow Government Prize for Young Scientists for a series of papers examining the role of microRNAs in the development and diagnosis of cancer, viral and inflammatory diseases, and preeclampsia.