Tea polyphenol protects against cisplatin-induced meiotic defects in porcine oocytes.

Changyin Zhou,Xiayan Shiyang,Huili Wang,Xue Zhang,Bo Xiong

doi:10.18632/aging.102084

Changyin Zhou, Xiayan Shiyang + Show 3 more

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https://doi.org/10.18632/aging.102084

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Abstract

DDP (cisplatin), a DNA cross-linking agent, is one of the most common chemotherapeutic drugs that have been widely used in the treatment of sarcomas and germ cell tumors. DDP treatment exhibits severe side effects including renal toxicity, ototoxicity and embryo-toxicity. Women of reproductive age treated with DDP may lead to loss of primordial follicles, resulting in the depletion of the ovarian reserve and consequent premature ovarian failure. However, the influence of DDP on the oocyte quality and the strategy to prevent it has not yet fully clarified. Here, we report that DDP exposure resulted in the oocyte meiotic failure via disrupting the meiotic organelle dynamics and arrangement, exhibiting a prominently impaired cytoskeleton assembly, including spindle formation and actin polymerization. In addition, exposure to DDP led to the abnormal distribution of mitochondrion and cortical granules, two indicators of cytoplasmic maturation of oocytes. Conversely, TP (tea polyphenols) supplementation partially restored all of the meiotic defects resulted from DDP exposure through suppressing the increase of ROS level and the occurrence of DNA damage as well as apoptosis.

Highlights

Cisplatin (DDP) was first described by Michele Peyrone in 1845, and its structure was determined in 1893 [1, 2]
After culturing for 44 h in vitro, we observed the developmental status of Cumulusoocyte complexes (COCs) and the proportion of polar body extrusion (PBE)
Quantitative data revealed that the proportion of PBE was reduced in a dose-dependent manner after DDP treatment compared with the controls

Summary

Introduction

Cisplatin (DDP) was first described by Michele Peyrone in 1845, and its structure was determined in 1893 [1, 2]. After a long time of investigation, Rosenberg found its potential role in inducing the death of tumor cells and in 1978 it was approved by the FDA as a drug for the treatment of testicular and ovarian cancer [2]. DDP has been widely applied to treat a couple of tumors, such as ovary, testes, gastric, head and neck, non-small cell lung, gallbladder and urinary bladder [3,4,5]. DDP is an alkylating agent capable of forming adducts with macromolecules, with N7 atoms of purine nucleobases, which results in interand intra-strand DNA cross-links [6, 7]. Experimental evidence has revealed that other mechanisms, such as the production of reactive oxygen species (ROS) and the activation of inflammatory pathways, may contribute to the DDP-induced apoptosis [9]

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