Overlapping sperm damages from vitamin B or D deficiency in mice: Insights into the role of clinical supplementations

In this study, the effect of 14 weeks of standard diet (controls) or folate and vitamin B12-free diet (VBD group) or vitamin D-free diet (VDD group) were assessed on mice testicular function, and sperm function. Vitamin D deprivation caused increased body weight with no effect from VBD confirming the calcium-independent role of vitamin D on body weight homeostasis. The two deprivations caused convergent damages including decreased testosterone, worsened Johnson scores, tubular differentiation index and spermatogenesis index, and serious worsening of sperm parameters and of sperm functional tests (DNA methylation, protamination, DNA damage and lipid peroxidation). From a metabolic point of view, the damage from both models converged on the one carbon cycle (methylations) and the transsulfuration pathway (GSH and antioxidant defences) and increased circulating homocysteine, although with different mechanisms: VBD appeared to hamper methylations due to lower ability to regenerate homocysteine to methionine whereas VDD appeared to interfere with homocysteine transsulfuration to cysteine and, thereafter, GSH. VDD also caused a huge paradox increase of vitamin B12, which was likely in a non-functional form and warrants further investigation. These findings strongly endorse the potential benefit of combined folate/B12 and vitamin D supplementation in infertile patients.