Cytoprotective Effects of Tauroursodeoxycholic Acid in Heat Stress-Induced Endoplasmic Reticulum Stress in Male Germ Cells

Saygılı, Suna Karadeniz; Özatik, Orhan; Özatik, Fikriye Yasemin; Koçak, Ahmet; Gündoğdu, Ayşe Çakır; Öztatlici, Mustafa; Ozbilgin, Mahmut Kemal

doi:10.14712/fb2026.0007

Fol. Biol., Online First article

https://doi.org/10.14712/fb2026.0007

Cytoprotective Effects of Tauroursodeoxycholic Acid in Heat Stress-Induced Endoplasmic Reticulum Stress in Male Germ Cells

Suna Karadeniz Saygılı¹

, Orhan Özatik¹

, Fikriye Yasemin Özatik²

, Ahmet Koçak¹

, Ayşe Çakır Gündoğdu¹

, Mustafa Öztatlici³

, Mahmut Kemal Ozbilgin⁴

¹Kutahya Health Sciences University, Faculty of Medicine, Department of Histology and Embryology, Kutahya, 43100, Turkiye
²Kutahya Health Sciences University, Faculty of Medicine, Department of Pharmacology, Kutahya, 43100, Turkiye
³Gaziantep Islamic Science and Technology University, Faculty of Medicine, Department of Histology and Embryology, Gaziantep, 27000, Turkiye
⁴Manisa Celal Bayar University, Faculty of Medicine, Department of Histology and Embryology, Manisa, 45000, Turkiye

Received January 12, 2026
Accepted February 24, 2026

Heat stress disrupts cellular homeostasis in cells by inducing protein misfolding, activating endoplasmic reticulum stress pathways and impairing cell survival mechanisms. The present study aimed to evaluate the cytoprotective effects of tauroursodeoxycholic acid (TUDCA) against heat stress-induced cellular damage in an in vitro spermatogonial GC1 cell model. The IC₅₀ concentration of TUDCA was determined by the MTT assay. GC1 cells were divided into four groups: control (GC1C), TUDCA-treated (GC1TUDCA), heat stress model (HSM; GC1HSM) and TUDCA-treated HSM (GC1HSMTUDCA). Standard culture conditions were used for GC1C. HSM group cells were incubated for 60 minutes at 43 °C. TUDCA groups of cells were treated with 200 µM TUDCA in culture media for 24 hours. Following the experiments, all groups were subjected to immunocytochemical staining with phosphorylated PERK (p-PERK) and C/EBP homologous protein (CHOP) antibodies, and immunoreactivity was evaluated using the H-Score system. The MTT assay determined the IC₅₀ value of TUDCA as 558 µM for GC1 cells, with 200 µM selected for subsequent experiments due to minimal cytotoxicity. Heat stress exposure was associated with a reduction in GC1 cell viability and an increase in p-PERK and CHOP expression compared with the GC1C group. In heat-stressed cells, TUDCA treatment was associated with a significant decrease in p-PERK and CHOP expression relative to the GC1HSM group. These results suggest that TUDCA might reduce the cellular reactions related to endoplasmic reticulum stress in heat-stressed GC1 spermatogonial cells under in vitro conditions.