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  3. Cadmium exposure causes trophoblast abnormal syncytization and endocrine dysfunction in preeclampsia

Cadmium exposure causes trophoblast abnormal syncytization and endocrine dysfunction in preeclampsia

  • Reprod Toxicol. 2025 Aug:135:108934. doi: 10.1016/j.reprotox.2025.108934.
Weilong Lin 1,  Xuemeng Li 1,  Xiangyou An 1,  Jiancai Yin 1,  Ziyan Zhao 1,  Xiaorui Yan 1,  Rong Xu 1,  Baojing Zhao 1,  Xue Du 1,  Huiru Cheng 1,  Zhen Yu 2,  Yuanyuan Yang 3
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 (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei, Anhui 230032, China.
  • 2 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 (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: yuzhendev@126.com.
  • 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 (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: wlj69513@sina.com.
PMID: 40300673 DOI: 10.1016/j.reprotox.2025.108934
Abstract

Introduction: Cadmium exposure increases the risk of preeclampsia. Present study aimed to explore the mechanism of abnormal syncytization of trophoblasts caused by cadmium exposure and its relationship with preeclampsia.

Methods: RT-PCR, Western blot and Hematoxylin-Eosin were used to detect syncytization in placenta. BeWo cells were treated with forskolin (50 μM) and CdCl2 (20 μM) to verify the mechanism through which cadmium exposure led to abnormal syncytization and cadmium exposure subsequently caused endocrine dysfunction of syncytiotrophoblast.

Results: Compared with normotension control, abnormal accumulation of syncytial knots was found in placenta of preeclampsia. Cell fusion rate was increased and gene expressions of GCM1, SYN-1, SYN-2, PLGF and β-hCG were elevated in FSK-treated cells. In BeWo cells co-treated with FSK and CdCl2 and in BeWo cells co-treated with FSK and GCM1 siRNA, cell fusion rate was decreased and gene expression of SYN-2 was reduced as compared with FSK-treated cells. Nuclear translocation level of GCM1 was lower in placenta of preeclampsia and BeWo cells co-treated with FSK and CdCl2. The mRNA level of GCM1 and β-hCG were decreased in CdCl2 treated JEG3 cells. The expression of sFlt1 was increased and the expression of PLGF was decreased in placenta of preeclampsia, CdCl2 treated and GCM1 siRNA transfected JEG3 cells. Compared with cells treated with CdCl2 and GCM1 siRNA, co-treatment with CdCl2 and GCM1 siRNA resulted in decreased expressions of β-hCG, PLGF and GCM1 and increased expression of sFlt1 in JEG3 cells.

Conclusion: The results indicated that cadmium exposure during pregnancy led to abnormal syncytization and endocrine dysfunction of trophoblasts and were related to the occurrence of preeclampsia.

Keywords

Cadmium; GCM1; Preeclampsia; Syncytization.

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