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
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
PMID: 37980977 DOI: 10.1016/j.fct.2023.114189
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.
Products