2. Academic Validation
  3. Carbendazim exposure inhibits mouse oocytes meiotic maturation in vitro by destroying spindle assembly

Carbendazim exposure inhibits mouse oocytes meiotic maturation in vitro by destroying spindle assembly

  • Food Chem Toxicol. 2023 Jul 26;179:113966. doi: 10.1016/j.fct.2023.113966.
Cong Ma 1,  Zhuonan Yang 1,  Shouxin Zhang 2,  Xueke Zhang 1,  Siyuan Wang 3,  Huiru Cheng 3,  Yang Liu 3,  Hongzhen Ruan 1,  Zuying Xu 1,  Chunmei Liang 3,  Dan Liang 4,  Zhiming Ding 5,  Yajing Liu 6,  Yunxia Cao 7
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China.
  • 2 Biochip Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China.
  • 3 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China.
  • 4 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Anhui Provincial Institute of Translational Medicine, No.81 Meishan Road, Hefei, 230032, China.
  • 5 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Anhui Provincial Institute of Translational Medicine, No.81 Meishan Road, Hefei, 230032, China. Electronic address: dingzhiming10@163.com.
  • 6 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Anhui Provincial Institute of Translational Medicine, No.81 Meishan Road, Hefei, 230032, China. Electronic address: yjl@ustc.edu.cn.
  • 7 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 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, 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No.81 Meishan Road, Hefei, 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, China; Anhui Provincial Institute of Translational Medicine, No.81 Meishan Road, Hefei, 230032, China. Electronic address: caoyunxia5972@ahmu.edu.cn.
PMID: 37506866 DOI: 10.1016/j.fct.2023.113966
Abstract

Successful fertilization and early embryonic development heavily depend on the quality of the oocytes. Carbendazim (CBZ), a broad-spectrum fungicide, is widely available in the environment and has adverse effects on organisms. The present study focused on exploring the potential reproductive toxicity of CBZ exposure by investigating its effects on the maturation of mouse oocytes. The results demonstrated that although no disruptions were observed in the G2/M stage transition for meiosis resumption, CBZ did hinder the polar body extrusion (PBE) occurring during oocyte maturation. Cell cycle distribution analysis revealed that CBZ exposure interfered with the meiotic process, causing oocytes to be arrested at the metaphase I (MI) stage. The subsequent investigation highlighted that CBZ exposure impeded the spindle assembly and chromosomal alignment, which was linked to a decline in the level of p-MAPK. Additionally, CBZ exposure adversely affected the kinetochore-microtubule (K-MT) attachment, leading to the persistent activation of the spindle-assembly checkpoint (SAC). The study further noticed a substantial rise in the acetylation of α-tubulin and a reduction in spindle microtubule stability in CBZ-treated oocytes. In addition, the distribution pattern of Estrogen Receptor alpha (ERα) was altered in oocytes treated with CBZ, with abnormal aggregation on the spindles. CBZ exposure also resulted in altered histone modifications. A notable finding from this research was that the meiotic maturation of some oocytes remained unaffected even after CBZ treatment. However, during the ensuing metaphase II (MII) stage, these oocytes displayed anomalies in their spindle morphology and chromosome arrangement and diminished ability to bind to the sperm. The observations made in this study underscore the potential for CBZ to disrupt the meiotic maturation of oocytes, leading to a decline in the overall quality of oocytes.

Keywords

Carbendazim; Histone modifications; Miosis; Oocyte; Spindle-assembly checkpoint.

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