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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive
Chen Chen1, Tingye Sun1,2, Mingru Yin1
1Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Abstract:
Oocyte activation induced by calcium oscillations is an important process in normal fertilization and subsequent embryogenesis. In the clinical-assisted reproduction, artificial oocyte activation (AOA) is an effective method to improve the clinical outcome of patients with null or low fertilization rate after ICSI. However, little is known about the effect of AOA on preimplantation embryo development in cases with normal fertilization by ICSI. Here, we used ionomycin at different concentrations to activate oocytes after ICSI with normal sperm and evaluated energy metabolism and preimplantation embryo development. We found that a high concentration of ionomycin increased the frequency and amplitude of calcium oscillation patterns, affecting the balance of mitochondrial energy metabolism, leading to increased reactive oxygen species (ROS) and decreased ATP. Eventually, it increases DNA damage and decreases blastocyst formation. In addition, the addition of vitamin C to the culture medium ameliorated the increase in ROS and DNA damage and rescued the abnormal embryo development caused by excessive ionomycin activation. This study provides a perspective that the improper application of AOA may have adverse effects on preimplantation embryo development. Thus, clinical AOA treatment should be cautiously administered.
Insights
Artificial oocyte activation (AOA) with excessive ionomycin negatively impacts embryo development by disrupting energy metabolism and increasing DNA damage. Vitamin C can mitigate these adverse effects, suggesting cautious clinical application of AOA.
Area of Science:
- Reproductive Biology
- Embryology
- Assisted Reproductive Technology
Background:
- Oocyte activation via calcium oscillations is crucial for fertilization and embryogenesis.
- Artificial oocyte activation (AOA) improves outcomes in cases of low fertilization after intracytoplasmic sperm injection (ICSI).
- The impact of AOA on preimplantation embryo development following normal fertilization by ICSI remains unclear.
Purpose of the Study:
- To investigate the effects of ionomycin-induced AOA on energy metabolism and preimplantation embryo development after ICSI with normal fertilization.
- To evaluate the protective role of vitamin C against potential AOA-induced developmental abnormalities.
Main Methods:
- Oocytes were activated using varying concentrations of ionomycin post-ICSI with normal sperm.
- Mitochondrial energy metabolism, reactive oxygen species (ROS) levels, ATP production, and DNA damage were assessed.
- Preimplantation embryo development, including blastocyst formation, was evaluated.
- The effect of vitamin C supplementation on mitigating ionomycin-induced damage was examined.
Main Results:
- High ionomycin concentrations amplified calcium oscillations, disrupting mitochondrial energy metabolism.
- This disruption led to increased ROS, decreased ATP levels, and elevated DNA damage.
- Consequently, blastocyst formation rates were reduced.
- Vitamin C supplementation ameliorated ROS and DNA damage, rescuing abnormal embryo development.
Conclusions:
- Improper application of AOA, particularly at high ionomycin concentrations, can adversely affect preimplantation embryo development.
- AOA may negatively impact energy metabolism and increase DNA damage in embryos resulting from normal fertilization.
- Clinical AOA should be administered cautiously, and protective agents like vitamin C may offer a therapeutic strategy.
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