Vitamin D Impact on Male Reproductive Health

Vitamin D is increasingly recognised as a pivotal regulator of male reproductive physiology through both genomic and non-genomic mechanisms. The active metabolite binds to high-affinity receptors in the testes, epididymis and spermatozoa, modulating gene expression and rapid signalling pathways that influence steroidogenesis, spermatogenesis, sperm motility and capacitation. Deficiency is now implicated in impaired testosterone synthesis, disrupted calcium homeostasis, increased oxidative stress and altered germ-cell development. Animal models have demonstrated that inadequate vitamin D status leads to defective testicular architecture, reduced sperm quality and lower reproductive success, while human observational studies link low circulating levels to hypogonadism, poorer semen parameters and diminished pregnancy rates. Given the global prevalence of hypovitaminosis D and its reversible nature, understanding these mechanisms has direct implications for screening strategies and therapeutic supplementation in men with subfertility and endocrine dysfunction.

Research from Nature Portfolio

Recent murine investigations have revealed that chronic vitamin D deficiency suppresses key enzymes of the transsulfuration pathway in the testis, leading to oxidative stress-mediated damage to seminiferous tubules and a sharp decline in testosterone levels. These changes occur partly independent of classical receptor signalling, highlighting alternative metabolic pathways in spermatogenic impairment. In an ageing rat model, vitamin D3 supplementation restored intratesticular levels of the hormone, up-regulated vitamin D receptor expression and down-regulated the receptor for advanced glycation end products, thereby improving antioxidant defences, promoting germ-cell proliferation and reducing apoptosis in senescent testes. Together, these studies define molecular targets through which vitamin D delays testicular senescence and preserves male fertility.

Vitamin D Impact on Male Reproductive Health publication trend

The graph below shows the total number of articles in vitamin d impact on male reproductive health across all publications each year (not limited to Nature Index journals).

Technical terms

Vitamin D receptor (VDR): A nuclear and membrane-bound receptor that mediates genomic and rapid non-genomic actions of the active vitamin D metabolite.

Transsulfuration pathway: A metabolic route in testicular cells converting homocysteine to cysteine, critical for antioxidant glutathione synthesis and redox balance.

Apoptosis: Programmed cell death process that, when dysregulated, impairs germ-cell survival and spermatogenic output.

Oxidative stress: An imbalance favouring reactive oxygen species over antioxidant defences, leading to lipid, protein and DNA damage in sperm and testicular tissues.

Capacitation: A series of biochemical changes enabling spermatozoa to fertilise an oocyte, dependent on calcium influx and membrane modifications.

References

1. The role of the transsulfuration pathway in spermatogenesis of vitamin D deficient mice. Scientific Reports (2023).
2. Calcium and vitamin D homoeostasis in male fertility.. Proceedings of The Nutrition Society (2023).
3. Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism. Reproductive Biology and Endocrinology (2009).
4. Vitamin D is associated with testosterone and hypogonadism in Chinese men: Results from a cross-sectional SPECT-China study. Reproductive Biology and Endocrinology (2015).
5. Association Between Vitamin D, Reproductive Hormones and Sperm Parameters in Infertile Male Subjects. Frontiers in Endocrinology (2018).
6. Vitamin D3 regulates apoptosis and proliferation in the testis of D-galactose-induced aged rat model. Scientific Reports (2019).
7. Males with low serum levels of vitamin D have lower pregnancy rates when ovulation induction and timed intercourse are used as a treatment for infertile couples: results from a pilot study. Reproductive Biology and Endocrinology (2015).
8. The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: a randomized, triple blind, placebo-controlled clinical trial. Reproductive Biology and Endocrinology (2021).
9. Stereological assessment of the effects of vitamin D deficiency on the rat testis. BMC Endocrine Disorders (2020).
10. Vitamin D and Male Reproduction: Updated Evidence Based on Literature Review. Nutrients (2022).