2. Academic Validation
  3. DECR1 deficiency activates a lipid peroxidation-mitocytosis-mitochondrial dysfunction axis in trophoblasts to promote preeclampsia

DECR1 deficiency activates a lipid peroxidation-mitocytosis-mitochondrial dysfunction axis in trophoblasts to promote preeclampsia

  • Free Radic Biol Med. 2026 Jul:250:1-15. doi: 10.1016/j.freeradbiomed.2026.03.049.
Qin Zhang 1,  Huilian Feng 2,  Ruixin Chen 3,  Yao Long 4,  Wei Chu 5,  Yiran Li 5,  Wei Dai 5,  Qi Yao 2,  Xin Luo 6,  Hui Li 7,  Hongbo Qi 8
Affiliations

Affiliations

  • 1 The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China.
  • 3 Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
  • 4 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China.
  • 5 Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China; Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China.
  • 6 The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
  • 7 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401147, China; NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing, 401147, China. Electronic address: [email protected].
  • 8 Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China; Joint International Research Laboratory of Reproduction & Development, Ministry of Education, Chongqing, 400016, China; The Innovation and Talent Recruitment Base of Maternal-Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: [email protected].
PMID: 41862008 DOI: 10.1016/j.freeradbiomed.2026.03.049
Abstract

Preeclampsia (PE) is a pregnancy disorder characterized by placental maladaptation and maternal hypertension, with oxidative stress and lipid peroxidation as central features. Here we identify 2,4-dienoyl-CoA reductase 1 (DECR1), the rate-limiting enzyme in the auxiliary β-oxidation of unsaturated fatty acids, as a key regulator of trophoblast lipid redox balance. DECR1 expression is reduced in placentas from patients with late-onset preeclampsia (LOPE) and an L-NAME-induced PE mouse models. Genetic or pharmacological inhibition of DECR1 increases PUFA-rich lipid accumulation, enhances lipid peroxidation, and induces mitochondrial dysfunction, leading to loss of membrane potential, Reactive Oxygen Species buildup, ATP depletion, and impaired trophoblast migration and invasion. In vivo, DECR1 inhibition causes hypertension, renal injury, fetal growth restriction, and defective placental vascular remodeling. Mechanistically, DECR1 loss disrupts mitochondrial quality control by suppressing mitocytosis, effects that are reversed by radical-trapping agents or mitochondria-targeted Antioxidants. Liproxstatin-1 treatment restores maternal, fetal, and placental homeostasis. These findings define a DECR1-lipid peroxidation-mitochondria axis that maintains trophoblast function and placental adaptation, highlighting DECR1 as a potential therapeutic target for PE.

Keywords

DECR1; Lipid peroxidation; Preeclampsia.

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