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Updated: Nov 28, 2025
Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
Coping with DNA Double-Strand Breaks via ATM Signaling Pathway in Bovine Oocytes
Lili Wang1, Xiaolei Xu1, Mingming Teng1
1Shaanxi Stem Cell Engineering and Technology Research Center, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Abstract:
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 p21 in bovine oocytes. At the same time, the maturation rate of bovine oocytes decreased with a gradual increase in Zeocin dose, and the p21 expression in those immature oocytes changed significantly with the gradual increase in Zeocin dose (same as increased DSB intensity). Same as p21, the variation trend of ATM 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 ATM 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.
Insights
Oocyte DNA double-strand break (DSB) repair mechanisms are crucial for fertilization. Studies suggest ATM regulates the p53-p21 pathway, impacting meiosis completion and oocyte maturation.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- DNA double-strand breaks (DSBs) are common cellular injuries, particularly relevant in oocytes during meiosis I.
- Unlike somatic cells, oocyte DSBs primarily impact fertilization ability rather than cancer risk.
- Understanding DSB repair in oocytes is critical, especially with superimposed medically induced damage.
Purpose of the Study:
- To investigate the mechanisms of DNA double-strand break (DSB) repair in bovine oocytes during meiosis I.
- To explore the role of the ATM and p53-p21 pathway in oocyte response to DSB damage.
- To assess the impact of DSB intensity on oocyte maturation rates and gene expression.
Main Methods:
- Bovine oocytes were exposed to varying doses of Zeocin to induce DSBs.
- Quantitative analysis of p21 and ATM gene expression in response to DSB induction.
- Assessment of oocyte maturation rates correlated with DSB levels and gene expression.
Main Results:
- Oocyte maturation rates decreased with increasing Zeocin dose (DSB intensity).
- p21 and ATM gene expression levels significantly changed with increasing DSB intensity.
- Bovine oocytes exhibit tolerance to DSBs up to a certain threshold, beyond which maturation is impaired.
Conclusions:
- ATM may regulate the p53-p21 pathway to influence meiotic completion in oocytes.
- Oocyte response to DSBs involves tolerance but is compromised above a damage threshold.
- Nonhomologous recombination and cumulus cells may play roles in oocyte DSB repair pathways.
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