2. Academic Validation
  3. Cadmium induces spontaneous abortion by impairing endometrial stromal cell decidualization

Cadmium induces spontaneous abortion by impairing endometrial stromal cell decidualization

  • Toxicology. 2025 Feb:511:154069. doi: 10.1016/j.tox.2025.154069.
Xue-Ke Zhang 1,  Xuan Li 1,  Xing-Xing Han 1,  Dong-Ying Sun 2,  Yu-Qin Wang 3,  Zi-Zhuo Cao 4,  Lu Liu 5,  Zi-Han Meng 6,  Guo-Jing Li 7,  Yu-Jie Dong 8,  Dan-Yang Li 9,  Xiao-Qing Peng 10,  Hui-Juan Zou 11,  Dong Zhang 12,  Xiao-Feng Xu 13
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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, 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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, 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.
  • 3 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, 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 Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 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 (Anhui Medical University), No 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 5 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 6 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 7 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; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 8 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, 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 Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 9 Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • 10 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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei, Anhui 230032, China.
  • 11 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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: hienjoyshine@aliyun.com.
  • 12 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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: dong.ray.zhang@ahmu.edu.cn.
  • 13 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; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address: xxf0550@126.com.
PMID: 39892737 DOI: 10.1016/j.tox.2025.154069
Abstract

Cadmium (Cd) is a toxic heavy metal with a high propensity to accumulate within the body, and Cd accumulation has been shown to cause organ damage. However, it is unclear whether Cd accumulation is a cause of impaired decidualization, which induces to spontaneous abortion (SA). In this study, we found that the decidual Cd concentration was increased in patients with SA and positively correlated with the occurrence of SA. The levels of two decidualization markers (Prolactin, PRL and insulin-like growth factor binding protein 1, IGFBP1) were reduced in the decidua of all-cause SA patients. Using 8-week ICR female mice, we further established a uterus-specific Cd accumulation mouse model and verified that Cd-accumulating mice had increased numbers of absorbed fetuses and defective decidualization. Finally, using in vitro-cultured human ENdometrial stromal cells (hEnSCs), we found that Cd accumulation significantly inhibited decidualization; and moreover, Cd treatment downregulated the regulatory genes upstream of PRL and IGFBP1 such as PGR, ESR1, ESR2 and FOXO1. This study suggests that Cd accumulation could produce impaired decidualization by downregulating the upstream regulators of PRL and IGFBP1, thereby increasing the risk of SA. Our study offered new possibilities for the prevention and treatment of spontaneous abortion.

Keywords

Cadmium; Decidualization; Endometrial stromal cell; Spontaneous abortion; Uterine specific accumulation.

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