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DJ-1 deficiency causes metabolic abnormality in ornidazole-induced asthenozoospermia
Yi Sun1,2, Xinping Sun3, Lianming Zhao4
1National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China.
Abstract:
Asthenozoospermia (AS), defined as low-motility spermatozoa in the ejaculate, is a frequent cause of human male infertility. DJ-1 (also known as PARK7), a protein highly associated with male sterility, binds to the mitochondrial complex I subunit to protect mitochondrial function. However, its involvement in spermatogenesis has not been fully elucidated. Previously, the levels of DJ-1 were shown to be significantly decreased in testicular tissues of rats with ornidazole (ORN)-induced AS. Here, we used a rat model to investigate the localization and expression levels of DJ-1 and its interacting NDUFS3 and NDUFA4 mitochondrial complex I subunits, as well as AS-induced metabolic alterations in testicular tissues. ORN significantly reduced the levels of DJ-1 in the nucleus of secondary spermatocytes, while increasing the expression of NDUFS3 in the cytoplasm of primary spermatocytes. Further, NDUFA4 showed higher expression after treatment with ORN. The principal ORN-induced changes in metabolic small molecules related to the accumulation of glucose, glutamine, and N-acetyl aspartate, enhancement of purine pathway, increase of the phosphatidic acid (PA) (18:0/18:1), phosphatidylethanolamine (PE) (16:0/18:1), and PA (18:0/20:4) lipid metabolites, and imbalance in the concentrations of Na+ and K+. However, we did not observe any abnormalities of certain small metabolic molecules and metal ions in semen samples from patients with AS. In conclusion, these results suggest that DJ-1 deficiency in testicular tissues might be closely related to the localization of NDUFS3 and content of NDUFA4, thus causing abnormalities in the mitochondrial energy metabolism and multiple other metabolic pathways.
Insights
DJ-1 deficiency in testicular tissue is linked to asthenozoospermia (AS), affecting mitochondrial function and metabolism. This study reveals DJ-1
Area of Science:
- Reproductive Biology
- Mitochondrial Biology
- Metabolomics
Background:
- Asthenozoospermia (AS), characterized by low sperm motility, is a primary cause of male infertility.
- DJ-1 (PARK7) is crucial for male fertility and mitochondrial protection, but its role in spermatogenesis is unclear.
- Previous studies indicated reduced DJ-1 levels in ornidazole-induced AS rat models.
Purpose of the Study:
- To investigate DJ-1 localization and expression, along with mitochondrial complex I subunits (NDUFS3, NDUFA4), in a rat model of AS.
- To identify metabolic alterations in testicular tissues associated with AS.
Main Methods:
- Utilized an ornidazole-induced asthenozoospermia rat model.
- Examined DJ-1, NDUFS3, and NDUFA4 expression and localization via techniques not specified.
- Performed metabolomic analysis on testicular tissues to identify altered small molecules and ions.
Main Results:
- Ornidazole treatment reduced DJ-1 in spermatocytes and altered NDUFS3 and NDUFA4 expression.
- Observed significant metabolic changes including glucose accumulation, enhanced purine metabolism, altered lipid profiles (PA, PE), and ion imbalances (Na+, K+).
- Did not find similar metabolic or ionic abnormalities in semen from human AS patients.
Conclusions:
- DJ-1 deficiency in testicular tissue correlates with altered NDUFS3 localization and NDUFA4 levels.
- These changes likely contribute to mitochondrial dysfunction and broader metabolic disruptions in AS.
- Testicular metabolic alterations in AS may differ from those observable in patient semen samples.
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