C-phycocyanin protects against obesity-associated type 2 diabetes-induced male fertility dysfunction via key enzyme regulation

The prevalence of male infertility is steadily increasing and has become a growing global health concern. The goal of this study is to evaluate the therapeutic potential of C-phycocyanin (CPC), a natural phycobiliprotein pigment extracted from Spirulina platensis (Sp), on male reproductive dysfunction in obese rats with type 2 diabetes (OB-T2D). Daily treatment was administered for 3 months. CPC at 300 mg kg-1 significantly reduced body weight (-35.6%) and blood glucose levels (-40.2%). It markedly suppressed seminal plasma inflammation by reducing leukocyte count and the activities of myeloperoxidase (MPO), phospholipase A2 (PLA2), and elastase (ELA) in seminal plasma by 77.3%, 63.1%, and 55.4%, respectively. CPC significantly improved sperm quality by increasing sperm concentration as well as the percentages of sperm viability and motility, while significantly reducing the percentage of sperm abnormalities. In parallel, CPC stimulated key fertility-related enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), adenosine triphosphatase (ATPase), prostatic acid phosphatase (PAP), lactate dehydrogenase (LDH), and adenosine deaminase (ADA), while downregulating phosphodiesterase (PDE). Moreover, CPC optimized seminal plasma composition by increasing fructose levels, modulating pH, and enhancing the activity of hyaluronidase (HYAL) and alkaline phosphatase (ALP). Seminal plasma antioxidant defense was strengthened via increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST); and reduced oxidative stress markers including total oxidant status (TOS), hydrogen peroxide (H2O2), and thiobarbituric acid reactive substances (TBARS). Therefore, CPC exerts a potent protective effect against OB-T2D-induced reproductive dysfunction by improving sperm parameters, enzymatic activity, and seminal antioxidant capacity.