Decreased function of fatty acid desaturase 1 is associated with placental foetal vascular malperfusion and highlights the key role of the maternal–foetal interface
Abstract
Background: Placental foetal vascular malperfusion (PFVM) is a chronic disorder characterised by impaired blood flow and abnormal vascular development, inducing adverse neonatal outcomes. Long chain polyunsaturated fatty acids (LC-PUFAs) play a crucial role in placenta health. We aimed to explore the role of genetic variation in LC-PUFA metabolism in PFVM risk as well as underlying mechanisms.
Methods: Associations were examined between two functional polymorphisms (rs174538 and rs174556) of the fatty acid desaturase 1 (FADS1) gene encoding the rate-limiting enzyme for LC-PUFA metabolism and PFVM among pregnant women (n = 646). Placental transcriptomes were correlated with PFVM and FADS1 genotypes. Various assays were performed in human umbilical vein endothelial cells and trophoblasts with FADS1 inhibitor and LC-PUFA interventions to characterise their function changes.
Findings: Low-function alleles of both polymorphisms were significantly associated with increased PFVM risk and decreased placental FADS1 transcription level. In placenta tissue, lower FADS1 expression is also associated with PFVM. PFVM-associated genes are enriched to pathways related to immune responses, apoptosis, and angiogenesis, which overlap with the genes and pathways associated with the risk alleles and demonstrate a cell-type enrichment to endothelial cells. In vitro, FADS1 inhibition impairs multiple functions of and interactions between endothelial and trophoblast cells. These impairments are reversed by LC-PUFA supplementation.
Interpretation: These findings highlight the impact of maternal LC-PUFA homoeostasis in placenta health and suggest that maternal FADS1 variants can potentially be an early diagnostic marker for PFVM. Our data supports PUFA metabolism as a precision therapeutic or preventive target to reduce placental dysfunction risk.
Funding: 10.13039/100000052NIH, 10.13039/100006710Wayne State University and 10.13039/100006534Michigan State University.
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BibTeX
@article{liu2026decreased,
title = {{Decreased function of fatty acid desaturase 1 is associated with placental foetal vascular malperfusion and highlights the key role of the maternal–foetal interface}},
author = {Zhenjie Liu and Ze Long and Stephanie Nartey and Li Tao and Shahrazad Saab and Robert Ty Partridge and Carolyn M. Salafia and Zheyun Peng and Yang Jiang and Tengfei Ma and Douglas Ruden and Nigel Paneth and Jean M. Kerver and Raina Nakova Fichorova and Wanqing Liu},
journal = {eBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2026.106517},
url = {https://doi.org/10.1016/j.ebiom.2026.106517},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Decreased function of fatty acid desaturase 1 is associated with placental foetal vascular malperfusion and highlights the key role of the maternal–foetal interface
AU - Zhenjie Liu
AU - Ze Long
AU - Stephanie Nartey
AU - Li Tao
AU - Shahrazad Saab
AU - Robert Ty Partridge
AU - Carolyn M. Salafia
AU - Zheyun Peng
AU - Yang Jiang
AU - Tengfei Ma
AU - Douglas Ruden
AU - Nigel Paneth
AU - Jean M. Kerver
AU - Raina Nakova Fichorova
AU - Wanqing Liu
PY - 2026
DA - 2026/10/17
JO - eBioMedicine
DO - 10.1016/j.ebiom.2026.106517
UR - https://doi.org/10.1016/j.ebiom.2026.106517
AB - Background: Placental foetal vascular malperfusion (PFVM) is a chronic disorder characterised by impaired blood flow and abnormal vascular development, inducing adverse neonatal outcomes. Long chain polyunsaturated fatty acids (LC-PUFAs) play a crucial role in placenta health. We aimed to explore the role of genetic variation in LC-PUFA metabolism in PFVM risk as well as underlying mechanisms. Methods: Associations were examined between two functional polymorphisms (rs174538 and rs174556) of the fatty acid desaturase 1 (FADS1) gene encoding the rate-limiting enzyme for LC-PUFA metabolism and PFVM among pregnant women (n = 646). Placental transcriptomes were correlated with PFVM and FADS1 genotypes. Various assays were performed in human umbilical vein endothelial cells and trophoblasts with FADS1 inhibitor and LC-PUFA interventions to characterise their function changes. Findings: Low-function alleles of both polymorphisms were significantly associated with increased PFVM risk and decreased placental FADS1 transcription level. In placenta tissue, lower FADS1 expression is also associated with PFVM. PFVM-associated genes are enriched to pathways related to immune responses, apoptosis, and angiogenesis, which overlap with the genes and pathways associated with the risk alleles and demonstrate a cell-type enrichment to endothelial cells. In vitro, FADS1 inhibition impairs multiple functions of and interactions between endothelial and trophoblast cells. These impairments are reversed by LC-PUFA supplementation. Interpretation: These findings highlight the impact of maternal LC-PUFA homoeostasis in placenta health and suggest that maternal FADS1 variants can potentially be an early diagnostic marker for PFVM. Our data supports PUFA metabolism as a precision therapeutic or preventive target to reduce placental dysfunction risk. Funding: 10.13039/100000052NIH, 10.13039/100006710Wayne State University and 10.13039/100006534Michigan State University.
SN - 2352-3964
ER -