Coping with DNA Double-Strand Breaks via ATM Signaling Pathway in Bovine Oocytes

• Main Authors: Lili Wang, Xiaolei Xu, Mingming Teng, Guimin Zhao, Anmin Lei
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: DNA double-strand breaks; <i>ATM</i>; <i>p21</i>; bovine oocyte; in vitro maturation
• Online Access: https://www.mdpi.com/1422-0067/21/23/8892
• ISSN: 1661-6596; 1422-0067

As a common injury almost all cells face, DNA damage in oocytes—especially double-strand breaks (DSBs), which occur naturally during the first meiosis phase (meiosis I) due to synaptic complex separation—affects the fertilization ability of oocytes, instead of causing cancer (as in somatic cells). The mechanism of oocytes to effectively repair DSB damage has not yet been clearly studied, especially considering medically induced DSBs superimposed on naturally occurring DSBs in meiosis I. It was found that maturation rates decreased or increased, respectively corresponding with overexpression or interference of <i>p21</i> in bovine oocytes. At the same time, the maturation rate of bovine oocytes decreased with a gradual increase in Zeocin dose, and the <i>p21</i> expression in those immature oocytes changed significantly with the gradual increase in Zeocin dose (same as increased DSB intensity). Same as <i>p21</i>, the variation trend of <i>ATM</i> expression was consistent with the gradual increase in Zeocin dose. Furthermore, the oocytes demonstrated tolerance to DSBs during meiosis I, while the maturation rates decreased when the damage exceeded a certain threshold; according to which, it may be that <i>ATM</i> regulates the p53–p21 pathway to affect the completion of meiosis. In addition, nonhomologous recombination and cumulus cells are potentially involved in the process by which oocytes respond to DSB damage.