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  2. Microcystin-LR prenatal exposure drives preeclampsia-like changes in mice by inhibiting the expression of TGF-β and VEGFA

Microcystin-LR prenatal exposure drives preeclampsia-like changes in mice by inhibiting the expression of TGF-β and VEGFA

  • Food Chem Toxicol. 2023 Nov 18:182:114189. doi: 10.1016/j.fct.2023.114189.
Meihong Guo 1 Pinru Yan 2 Mengjiao Zhu 2 Manhou Choi 2 Xinrui Li 2 Jiahao Huang 2 Jianghao Zou 2 Jintao Yuan 3 Weidong Ding 2 Dongmei Li 2 Xiaodong Han 2 Yong Wang 4 Jiang Wu 5
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: 602022350004@smail.nju.edu.cn.
  • 2 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China.
  • 3 The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, Jiangsu, 212300, China.
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: yongwang@nju.edu.cn.
  • 5 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: wujiang@nju.edu.cn.
Abstract

Microcystin-leucine-arginine (MC-LR) is widespread in the water and food, which has suspected to be associated with adverse pregnancy outcomes. In the present study, we aim to assess the interaction between MC-LR exposure and preeclampsia development and elucidate the molecular events involved. After exposure to MC-LR during pregnancy, the mice developed hypertension and proteinuria, the typical symptoms of preeclampsia. This was associated with decreased invasiveness of placental trophoblast and vascular dysplasia caused by MC-LR through down-regulating VEGFA and TGF-β expression via Akt/m-TOR/HIF-1α pathway. In addition, this conclusion has been confirmed in a case-control study. Significantly, the addition of Deferoxamine (DFM), a phosphorylated serine-threonine protein kinases (p-AKT) specific agonist, can antagonize the inhibitory effect of MC-LR on the expression of related proteins, which further ameliorate the migration and invasion ability of HTR-8/Svneo cells. To sum up, our study revealed the pathologic mechanism by which MC-LR lead to preeclampsia and emphasized the importance of pregnancy management.

Keywords

Angiogenesis; HTR-8/Svneo; Invasion; Microcystin-LR; Placenta; Preeclampsia; TGF-β; VEGFA.

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