biostudies-literatureUnknown1(1)Xu CInfertility is a global concern attributed to genetic defects, lifestyle, nutrition, and any other factors that affect the local metabolism and niche microenvironment of the reproductive system. 2-Oxoglutarate receptor 1 (OXGR1) is abundantly expressed in the testis; however, its cellular distribution and biological function of OXGR1 in the male reproductive system remain unclear. In the current study, we demonstrated that OXGR1 is primarily expressed in epididymal smooth muscle cells (SMCs). Aging and heat stress significantly reduced OXGR1 expression in the epididymis. Using OXGR1 global knockout and epididymal-specific OXGR1 knockdown models, we revealed that OXGR1 is essential for epididymal sperm maturation and fluid acid-base balance. Supplementation of α-ketoglutaric acid (AKG), theLife metabolism67-80https://www.ebi.ac.uk/biostudies/studies/S-EPMC11749693biostudies-literatureSmooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation.PMC11749693Gyawali IYang JShu GJiang QXu CTan CGuo SZhou YYi HWang SZhang YLu JJi YZhang CYuan YfalseSmooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation.Infertility is a global concern attributed to genetic defects, lifestyle, nutrition, and any other factors that affect the local metabolism and niche microenvironment of the reproductive system. 2-Oxoglutarate receptor 1 (OXGR1) is abundantly expressed in the testis; however, its cellular distribution and biological function of OXGR1 in the male reproductive system remain unclear. In the current study, we demonstrated that OXGR1 is primarily expressed in epididymal smooth muscle cells (SMCs). Aging and heat stress significantly reduced OXGR1 expression in the epididymis. Using OXGR1 global knockout and epididymal-specific OXGR1 knockdown models, we revealed that OXGR1 is essential for epididymal sperm maturation and fluid acid-base balance. Supplementation of α-ketoglutaric acid (AKG), the2022-01-01T00:00:00Z2022 Aug2025-04-21T23:57:11.253Z2025-04-05T19:21:25.129ZS-EPMC117496933987268310.1093/lifemeta/loac012