ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Comparative Analysis of Lipid Metabolism in Trophoblast Subpopulations in Preeclampsia and In Vitro Hypoxia Model
Provisionally accepted
- 1National Research University Higher School of Economics, Moscow, Russia
- 2Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Preeclampsia remains one of the leading causes of maternal and perinatal morbidity; however, its molecular mechanisms are not fully understood. The disease is known to be associated with lipid metabolism disturbances. In this study, we analyzed gene expression in three trophoblast subpopulations—VCT, SCT, and EVT—based on single-cell RNA-seq data from preeclamptic placentas and compared the results with the BeWo b30 cell model under chemically induced hypoxia. All trophoblast populations exhibited hypoxia accompanied by lipid metabolism reprogramming. In the syncytiotrophoblast (SCT), the main barrier between the maternal bloodstream and the fetus, preeclampsia was associated with a significant decrease in the expression of LDLR and cholesterol biosynthesis genes (OR = 4.991, p = 6.30e−04). At the same time, we observed increased expression of genes related to transcytosis (SCARB1, CAV1). In the extravillous trophoblast (EVT), in contrast, Low-density Lipoprotein Receptor (LDLR) expression was elevated, while cholesterol biosynthesis genes were downregulated. Hypoxia modeling in BeWo b30 cells reproduced the changes characteristic of the SCT subpopulation, including a fivefold increase in PCSK9 expression (padj = 3.53e−10) and a 1.5-fold decrease in SNX17 (padj = 1.76e−04)—key regulators of exogenous lipoprotein uptake in trophoblasts. Simultaneously, we observed suppression of lipid biosynthesis genes and activation of transcription of genes associated with transcytosis and cholesterol efflux. These results confirm the pivotal role of hypoxic stress in lipid metabolism disruption and reveal subpopulation-specific trophoblast reprogramming in preeclampsia, including a shift from endocytosis to transcytosis, which likely serves as a compensatory mechanism to ensure fetal lipid supply under limited availability.
Keywords: Preeclampsia, trophoblast, Lipid Metabolism, hypoxia, single-cell RNA-seq, SCARB1, pcsk9
Received: 23 Oct 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Antipenko, Knyazev, Kulagin and Tonevitsky. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ivan Antipenko, vantip22813@gmail.com
Alexander Tonevitsky, atonevitsky@hse.ru
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.