Abstract
BACKGROUND: Vitamin D is metabolised throughout the male reproductive system, suggesting a direct regulatory role of vitamin D in male reproduction. OBJECTIVES: To investigate the association between plasma vitamin D levels at sperm ejaculation and during spermatogenesis and biomarkers of male fecundity in young men. MATERIALS AND METHODS: From the Fetal Programming of Semen Quality cohort, Denmark, 2017-2019, 1047 young men provided a semen and a blood sample, and self-measured their testes volume at a clinical visit. Plasma levels of vitamin D (25(OH)D(3)) and reproductive hormones were measured in the blood sample. Relative percentage differences in semen characteristics, testes volume and reproductive hormone levels were analysed according to measured vitamin D levels (categorised, continuous and as restricted cubic splines) at sperm ejaculation. Additionally, we used the seasonal variation in endogenous vitamin D synthesis to estimate individual vitamin D levels 3 months prior to sperm ejaculation (at initiation of spermatogenesis) in addition to 2 and 1 month before. This was analysed following the same strategy. RESULTS: Compared to measured vitamin D levels >75 nmol/L, levels <25 nmol/L at sperm ejaculation were associated with lower total sperm count (‒15% [95% confidence interval: ‒33%; 8%]), and a higher proportion of non-progressive and immotile spermatozoa (11% [95% confidence interval: 0%; 24%]). Lower measured vitamin D levels were also associated with higher oestradiol, lower sex hormone-binding globulin and lower follicle-stimulating hormone, in dose-dependent manners. Vitamin D levels estimated before and during spermatogenesis yielded similar associations as vitamin D levels measured at sperm ejaculation. DISCUSSION: By using the seasonal variation in endogen vitamin D synthesis, we were able to estimate individual vitamin D levels during spermatogenesis. CONCLUSION: Lower vitamin D levels before and during spermatogenesis and at sperm ejaculation were associated with lower total sperm count and sperm motility and an altered reproductive hormone profile.