2. Academic Validation
  3. Triphenyltin chloride exposure inhibits meiotic maturation of mouse oocytes by disrupting cytoskeleton assembly and cell cycle progression

Triphenyltin chloride exposure inhibits meiotic maturation of mouse oocytes by disrupting cytoskeleton assembly and cell cycle progression

  • Toxicol In Vitro. 2024 Jun:98:105834. doi: 10.1016/j.tiv.2024.105834.
Cong Ma 1,  Hongzhen Ruan 2,  Huiru Cheng 3,  Zuying Xu 2,  Caiyun Wu 2,  Dan Liang 3,  Huifen Xiang 4,  Yunxia Cao 5,  Zhiming Ding 6
Affiliations

Affiliations

  • 1 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China.
  • 2 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China.
  • 3 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China.
  • 4 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China. Electronic address: huifen521@sina.com.
  • 5 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China. Electronic address: caoyunxia5972@ahmu.edu.cn.
  • 6 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei 230032, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei 230022, China. Electronic address: dingzhiming10@163.com.
PMID: 38657713 DOI: 10.1016/j.tiv.2024.105834
Abstract

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts Cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation.

Keywords

Meiosis; Oocyte; SAC; Spindle; Triphenyltin chloride.

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