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Mediating effect of ROS on mtDNA damage and low ATP content induced by arsenic trioxide in mouse oocytes
Wenya Zhang1, Yingxia Liu, Zhen An
1School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Abstract:
Mitochondria provide most of the adenosine triphosphates (ATP) necessary for the maturation of oocytes. Various environmental toxicants would lead damage to mitochondrial DNA (mtDNA) and hence interfere with oocytes development. In the current study, the effect of arsenic trioxide (As2O3) on the common 3867 bp deletion and the copy number of mtDNA in mitochondria of mouse oocytes in vivo or in vitro, as well as the molecular pathway leading to the damage were investigated. PCR strategy was used to detect the damage of mtDNA. Reactive oxygen species (ROS) and ATP content in oocytes were checked to determine the influence of As2O3 on oxidative stress and activity of mitochondria. The results showed that As2O3 could obviously decrease the copy number of mtDNA and cause severe 3867 bp deletion in mitochondria together with elevated ROS level, while ATP content was decreased. Co-treatment with N-Acetyl-Cysteine (NAC) efficiently eliminated ROS induced by As2O3, lessened the mtDNA damage and enhanced ATP content in mouse oocytes both in vivo and in vitro. Taken together, the present study revealed that As2O3 could cause severe mtDNA damage and decrease ATP content by inducing excessive ROS, and this damage would then probably restrain the further development of mouse oocytes.
Insights
Arsenic trioxide (As2O3) damages mouse oocyte mitochondrial DNA (mtDNA), reducing ATP levels by increasing reactive oxygen species (ROS). N-Acetyl-Cysteine (NAC) mitigates this damage, preserving oocyte development.
Area of Science:
- Reproductive Biology
- Mitochondrial Biology
- Toxicology
Background:
- Mitochondria are crucial for oocyte maturation, producing adenosine triphosphates (ATP).
- Environmental toxicants can damage mitochondrial DNA (mtDNA), impairing oocyte development.
- Arsenic trioxide (As2O3) is an environmental toxicant with potential effects on reproductive cells.
Purpose of the Study:
- To investigate the impact of arsenic trioxide (As2O3) on mouse oocyte mitochondrial DNA (mtDNA) integrity and copy number.
- To elucidate the molecular pathway, specifically the role of reactive oxygen species (ROS), in As2O3-induced mtDNA damage.
- To evaluate the protective effect of N-Acetyl-Cysteine (NAC) against As2O3 toxicity in mouse oocytes.
Main Methods:
- Polymerase Chain Reaction (PCR) was employed to detect mtDNA deletions.
- Measurement of reactive oxygen species (ROS) levels and ATP content in oocytes.
- In vivo and in vitro studies using mouse oocytes, with and without As2O3 and NAC co-treatment.
Main Results:
- As2O3 significantly reduced mtDNA copy number and induced a common 3867 bp deletion in mouse oocytes.
- As2O3 exposure led to increased ROS levels and decreased ATP content, indicating oxidative stress and impaired mitochondrial function.
- Co-treatment with NAC effectively reduced ROS, protected against mtDNA damage, and restored ATP levels in oocytes.
Conclusions:
- Arsenic trioxide (As2O3) causes significant mitochondrial DNA (mtDNA) damage and reduces ATP production in mouse oocytes, primarily through the induction of excessive reactive oxygen species (ROS).
- This As2O3-induced damage likely hinders the developmental potential of mouse oocytes.
- N-Acetyl-Cysteine (NAC) demonstrates a protective role against As2O3 toxicity by scavenging ROS and preserving mitochondrial function and mtDNA integrity.
