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

Yu-Feng Zhang, Hua-Long Zhu, Xiao-Feng Xu, Jin Zhang, Qing Ling, Shuang Zhang, Wei Chang, Yong-Wei Xiong, De-Xiang Xu, Hua Wang

Environmental pollution (Barking, Essex : 1987) 2023 Jul 01

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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. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Yu-Feng Zhang, Hua-Long Zhu, Xiao-Feng Xu, Jin Zhang, Qing Ling, Shuang Zhang, Wei Chang, Yong-Wei Xiong, De-Xiang Xu, Hua Wang. Activation of Atg5-dependent placental lipophagy ameliorates cadmium-induced fetal growth restriction. Environmental pollution (Barking, Essex : 1987). 2023 Jul 01;328:121602