Vitamin D co-administration mitigates testicular and sperm dysfunction in high fat diet- induced obese mouse model

Obesity, which is mostly related to high fat diet (HFD) consumption, could impair male reproductive function. How vitamin D (VD) co-administration ameliorates male reproductive dysfunction during obesity development is not fully understood. Therefore, this study aims to investigate the effect of VD co-administered with HFD on testicular and sperm functions in mice and to unravel the underlying mechanisms involved.

Adult male ICR mice were given HFD with VD (HFDVD+) or without VD (HFDVD-), orally for 12 consecutive weeks. Immediately following sacrifice, blood was withdrawn and testes and epididymal sperm were harvested.

HFDVD+ mice exhibited higher serum testosterone, FSH, and LH levels, higher expression of testicular VD receptor (VDR), retinoic acid receptor (RXR α/β/γ) and VD metabolizing enzymes (CYP27B1), testicular steroidogenic proteins (StAR, CYP11A1, 3β-HSD, 17β-HSD, CYP17A1, SF-1 except testicular aromatase), testicular spermatogenic proteins (PLZF, SOX9, SIRT1, AR, SMAD5, ER-α) and blood-testis barrier proteins (occludin, ZO-2, vimentin, connexin-43, N-cadherin) when compared to HFDVD- mice. Additionally, upregulation of testicular RANK and RANKL proteins and downregulation of testicular OPG protein were ameliorated in HFDVD+ mice. Epididymal sperm analysis revealed improvement in sperm parameters in HFDVD+ mice which positively correlated with serum VD levels. In HFDVD+ mice sperm, lesser downregulation of VDR, mitochondrial proteins (TOMM20, ATPB, COX IV), junctional adhesion molecule-A (JAM-A), and glucose transporter 1 (GLUT1) expression were observed.

Co-administration of VD with HFD helps to ameliorate testicular and sperm dysfunctions during obesity development, suggesting VD role in overcoming male reproductive impairment in obesity.