Abstract
Seminal vesicle integrity supports semen composition and sperm function, whereas type 2 diabetes mellitus can induce atrophy and fibrosis in this organ. Using a high-fat diet/streptozotocin-induced model in male mice and primary mouse seminal vesicle epithelial cells exposed to high glucose, we assessed fibrotic remodeling, lipid metabolism, PPARα/PGC-1α signaling, endoplasmic reticulum stress, and apoptosis through histological, biochemical, and lipidomic analyses. Diabetic seminal vesicles showed atrophy and fibrosis together with altered lipid profiles, free fatty acid accumulation, reduced PPARα/PGC-1α expression, and increased IRE1-associated stress and apoptosis. Levocarnitine attenuated these changes in vivo and reduced profibrotic responses in vitro. PPARα overexpression reproduced several protective effects, whereas IRE1 inhibition reduced stress-associated injury without restoring PPARα/PGC-1α signaling. These findings identify metabolic dysregulation and endoplasmic reticulum stress as associated features of diabetic seminal vesicle remodeling and support further evaluation of levocarnitine for diabetes-associated reproductive tract injury.