Activation of Atg5-dependent placental lipophagy ameliorates cadmium-induced fetal growth restriction

  • Environ Pollut. 2023 Apr 7;121602. doi: 10.1016/j.envpol.2023.121602.
Yu-Feng Zhang  1 ,  Hua-Long Zhu  1 ,  Xiao-Feng Xu  2 ,  Jin Zhang  1 ,  Qing Ling  1 ,  Shuang Zhang  1 ,  Wei Chang  1 ,  Yong-Wei Xiong  1 ,  De-Xiang Xu  3 ,  Hua Wang  4
Affiliations
  • 1. Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China.
  • 2. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui, China.
  • 3. Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, China.
  • 4. Department of Toxicology, School of Public Health, Anhui Medical University, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, China. Electronic address: [email protected].
PMID: 37031847 DOI: 10.1016/j.envpol.2023.121602
Abstract

Cadmium (Cd), an environmental contaminant, can result in placental non-selective Autophagy activation and fetal growth restriction (FGR). However, the role of placental lipophagy, a selective Autophagy, in Cd-induced FGR is unclear. This work uses case-control study, animal experiments and cultures of primary human placental trophoblast cells to explore the role of placental lipophagy in Cd-induced FGR. We found association of placental lipophagy and all-cause FGR. Meanwhile, pregnancy Cd exposure induced FGR and placental lipophgay. Inhibition of placental lipophagy by pharmacological and genetic means (Atg5-/- mice) exacerbated Cd-caused FGR. Inversely, activating of placental lipophagy relieved Cd-stimulated FGR. Subsequently, we found that activation of Atg5-dependent lipophagy degrades lipid droplets to produce free Cholesterol, and promotes placental progesterone (P4) synthesis. Gestational P4 supplementation significantly reversed Cd-induced FGR. Altogether, activation of Atg5-dependent placental lipophagy ameliorates Cd-induced FGR.

Keywords
Atg5; Cadmium; Fetal growth restriction; Lipophagy; Progesterone.
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