ReviewPossible influence of vitamin D on male reproduction

- VDR and vitamin D metabolizing enzymes are expressed in the reproductive organs.
- VDR induces non-genomic effects in high quality spermatozoa.
- Vitamin D regulates aromatase and estradiol signaling in testis and epididymis.
- Serum 25-OHD is associated with semen quality and sex steroid production.
- Vitamin D may induce differentiation of testicular germ cell cancer.

Vitamin D is a versatile signaling molecule with an established role in the regulation of calcium homeostasis and bone health. In recent years the spectrum of vitamin D target organs has expanded and a reproductive role is supported by the presence of the vitamin D receptor (VDR) and the vitamin D metabolizing enzymes in the gonads, reproductive tract, and human spermatozoa. Interestingly, expression levels of VDR and the vitamin D inactivating enzyme CYP24A1 in human spermatozoa serve as positive predictive markers of semen quality and are higher expressed in spermatozoa from normal than infertile men. VDR mediates a non-genomic increase in intracellular calcium concentration, sperm motility, and induces the acrosome reaction. Furthermore, functional animal model studies have shown that vitamin D is important for sex steroid production, estrogen signaling, and semen quality. Cross-sectional clinical studies have supported the notion of a positive association between serum 25-hydroxyvitamin D (25-OHD) level and semen quality in both fertile and infertile men. However, it remains to be determined whether this association reflects a causal effect. The VDR is ubiquitously expressed and activated vitamin D is a regulator of insulin, aromatase, and osteocalcin. Hence, it is plausible that the influence of vitamin D on gonadal function may be mediated indirectly through other vitamin D regulated endocrine factors. Recent studies have indicated that vitamin D supplementation may be beneficial for couples in need of assisted reproductive techniques as high serum vitamin D levels were found to be associated with a higher chance of achieving pregnancy. Randomized clinical trials are needed to determine whether systemic changes in vitamin D metabolites can influence semen quality, fertility, and sex steroid production in infertile men. In this review known and possible future implications of vitamin D in human male reproduction function will be discussed.