The mitochondrial signature of sperm motility loss: a study of mitophagy and apoptosis in asthenozoospermia
Journal of Assisted Reproduction and Genetics, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10815-026-03867-5
- Dergi Adı: Journal of Assisted Reproduction and Genetics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
- Anahtar Kelimeler: Apoptosis, Asthenozoospermia, ATG5, Mitophagy, Oxidative stress
- İstanbul Medipol Üniversitesi Adresli: Evet
Özet
Purpose: To investigate whether mitophagy contributes to the pathophysiology of asthenozoospermia through its association with apoptosis and oxidative stress, and to elucidate potential mechanisms underlying impaired sperm motility. Methods: This controlled study included a total of 60 semen samples collected from male patients between 2023 and 2024. Participants were categorized into asthenozoospermic (A, n = 30) and normozoospermic (N, n = 30) groups based on sperm motility, according to WHO criteria. The expression of ATG5 and cyt-c was examined using immunofluorescence and western blotting. Mitochondrial membrane potential (MMP) was measured with JC-1 dye, and oxidative stress markers (MDA and AOPP) were quantified in seminal plasma. Transmission electron microscopy was performed to evaluate mitochondrial ultrastructure. Results: Sperm with preserved MMP were significantly reduced in the asthenozoospermic group (p < 0.0001, d = 2.12). Elevated MDA (p < 0.0001, d = 2.58) and AOPP (p < 0.0001, r = 0.71) levels seen in asthenozoospermic group are indicative of increased oxidative stress. ATG5 and cyt-c expression levels were significantly higher in astehenozoospermic sperm (p = 0.003, d = 1.38; p = 0.0003, r = 0.51, respectively), and a strong correlation was found between these two markers in both groups (N, p < 0.0001; A, p = 0.0002). However, no significant correlation was found between mitophagy/apoptosis markers and oxidative stress levels. Ultrastructural examination revealed mitochondrial damage and autophagosome-like structures in asthenozoospermic samples. Conclusions: Asthenozoospermia is characterized by increased mitophagy and apoptosis independent of MDA and AOPP, suggesting impaired mitochondrial quality control as a potential mechanism for reduced sperm motility. These findings provide insights into the molecular basis of sperm dysfunction and support further research into mitochondrial-targeted strategies for managing asthenozoospermia.