Lipid profile of circulating placental extracellular vesicles during pregnancy identifies foetal growth restriction risk

Author:

Klemetti Miira M.12,Pettersson Ante B. V.3,Ahmad Khan Aafaque4,Ermini Leonardo1,Porter Tyler R.1,Litvack Michael L.3,Alahari Sruthi1,Zamudio Stacy5,Illsley Nicholas P.5,Röst Hannes4,Post Martin367,Caniggia Isabella1267ORCID

Affiliation:

1. Lunenfeld‐Tanenbaum Research Institute Mount Sinai Hospital Toronto Ontario Canada

2. Department of Obstetrics & Gynecology University of Toronto Toronto Ontario Canada

3. Program in Translational Medicine, Peter Gilgan Centre for Research and Learning Hospital for Sick Children Toronto Ontario Canada

4. Donnelly Centre for Cellular and Biomolecular Research University of Toronto Toronto Canada

5. Placental Research Group LLC Maplewood New Jersey USA

6. Institute of Medical Science University of Toronto Toronto Ontario Canada

7. Department Physiology University of Toronto Toronto Ontario Canada

Abstract

AbstractSmall‐for‐gestational age (SGA) neonates exhibit increased perinatal morbidity and mortality, and a greater risk of developing chronic diseases in adulthood. Currently, no effective maternal blood‐based screening methods for determining SGA risk are available. We used a high‐resolution MS/MSALL shotgun lipidomic approach to explore the lipid profiles of small extracellular vesicles (sEV) released from the placenta into the circulation of pregnant individuals. Samples were acquired from 195 normal and 41 SGA pregnancies. Lipid profiles were determined serially across pregnancy. We identified specific lipid signatures of placental sEVs that define the trajectory of a normal pregnancy and their changes occurring in relation to maternal characteristics (parity and ethnicity) and birthweight centile. We constructed a multivariate model demonstrating that specific lipid features of circulating placental sEVs, particularly during early gestation, are highly predictive of SGA infants. Lipidomic‐based biomarker development promises to improve the early detection of pregnancies at risk of developing SGA, an unmet clinical need in obstetrics.

Funder

Canada Research Chairs

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

Wiley

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