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

Document Type

Article

Publication Date

2026

Abstract

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. Methods: 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 Immediately following sacrifice, blood was withdrawn and testes and epididymal sperm were harvested. Results: 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. Conclusion: 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.

Keywords

Vitamin D, Obesity, Testes, Sperm, Steroidogenesis, Spermatogenesis

Publication Title

Journal of Steroid Biochemistry and Molecular Biology

ISSN

0960-0760

DOI

10.1016/j.jsbmb.2025.106910

Volume

257

First Page

106910

Publisher

Elsevier

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