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  3. Cadmium exposure activates mitophagy through downregulating thyroid hormone receptor/PGC1α signal in preeclampsia

Cadmium exposure activates mitophagy through downregulating thyroid hormone receptor/PGC1α signal in preeclampsia

  • Ecotoxicol Environ Saf. 2024 May:276:116259. doi: 10.1016/j.ecoenv.2024.116259.
Zhen Yu 1,  Tao Yu 1,  Xuan Li 1,  Weilong Lin 1,  Xuemeng Li 1,  Muxin Zhai 1,  Jiancai Yin 1,  Li Zhao 1,  Xiaoyu Liu 1,  Baojing Zhao 1,  Cancan Duan 1,  Huiru Cheng 1,  Fen Wang 2,  Zhaolian Wei 3,  Yuanyuan Yang 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Key Laboratory of Population Health Across Life Cycle, Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Provincial Institute of Translational Medicin (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China.
  • 2 Department of Geriatric Endocrinology, The First Affiliated Hospital of Anhui25 Medical University, Hefei 230032, China.
  • 3 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Key Laboratory of Population Health Across Life Cycle, Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Provincial Institute of Translational Medicin (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: weizhaolian_1@126.com.
  • 4 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Key Laboratory of Population Health Across Life Cycle, Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Provincial Institute of Translational Medicin (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: wlj69513@sina.com.
PMID: 38581905 DOI: 10.1016/j.ecoenv.2024.116259
Abstract

Gestational cadmium exposure increases the risk of preeclampsia. Placenta Mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced Mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative Real-Time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced Mitophagy. Mitophagy marker LC3BII/I and p62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and p62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and p62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and p62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta Mitophagy through downregulation of Thyroid Hormone Receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.

Keywords

Cadmium; Mitophagy; PGC1α; Preeclampsia; Thyroid hormone receptor.

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