Targeting the Nicotine-driven Maladaptive ER Stress Axis: Protective Roles of Melatonin and Coenzyme Q10 in Rat Testis
Reproductive Sciences, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s43032-026-02235-z
- Dergi Adı: Reproductive Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: Coenzyme Q10, Endoplasmic reticulum stress, Melatonin, Nicotine, Sperm, Testis
- Erciyes Üniversitesi Adresli: Evet
Özet
The endoplasmic reticulum (ER) plays a pivotal role in protein folding and cellular homeostasis and is highly sensitive to oxidative stress. Nicotine is a potent pro-oxidant; however, its effects on ER stress signaling in testicular tissue and the protective potential of melatonin and coenzyme Q10 (CoQ10) remain insufficiently defined. This study investigated nicotine-induced sperm dysfunction and the involvement of oxidative stress-mediated ER stress pathways in rat testes. Two-month-old male Wistar albino rats (n = 48) were assigned to control, nicotine, nicotine + melatonin, nicotine + CoQ10, nicotine + melatonin + CoQ10, and melatonin + CoQ10 groups. Sperm quality was evaluated, and testicular tissue was analyzed for oxidative stress markers, ER stress-related gene expression, histopathological alterations, and immunohistochemical localization of proteins. Nicotine exposure significantly impaired sperm motility and membrane integrity and increased abnormal morphology, mortality, and apoptosis (p < 0.001). These effects were associated with elevated lipid peroxidation and depletion of antioxidant defenses, including reduced glutathione, glutathione peroxidase, and catalase (p < 0.001). Melatonin and/or CoQ10 partially restored sperm quality and antioxidant capacity. Moreover, antioxidant treatment significantly downregulated ER stress-associated genes (Activating transcription factor 4-ATF4; Activating transcription factor 6-ATF6; C/EBP homologous protein-CHOP; 78 kDa glucose-regulated protein-GRP78; inositol-requiring enzyme 1 alpha-IRE1α; and protein kinase RNA-like endoplasmic reticulum kinase-PERK) and reduced CHOP immunoreactivity, while CoQ10 selectively enhanced XBP-1 immunoreactivity. In conclusion, nicotine-induced testicular dysfunction is mediated by oxidative stress-driven ER stress activation, whereas melatonin and CoQ10 confer protection through modulation of redox balance and ER stress signaling.