Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: Transient receptor potential vanilloid 5/6 (TRPV5/6), sodium/calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm-oocyte binding. In humans, seminal calcium concentration between 5-10 mM was associated with a higher fraction of motile and morphologically normal sperm cells and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.
Context Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. Objective Determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. Design A single-center, double-blinded, randomized clinical trial (NCT01304927), 307 infertile men were randomized (1:1) to a single dose of 300,000 IU cholecalciferol followed by 1,400 IU cholecalciferol + 500 mg of calcium daily (n=151) or placebo (n=156) for 150 days. Reported metabolic parameters including fasting plasma glucose, HbA1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols and triglyceride were secondary endpoints. The primary endpoint semen quality has previously been reported. Results Men receiving vitamin D supplementation improved their vitamin D status, while vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone (PTH). At end of trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs. 74 pmol/L, P = 0.018) and 19% lower HOMA-IR (2.2 vs. 2.7, P = 0.025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs. 1.32 mmol/L, P = 0.008) compared with the placebo group. Conclusion High-dose vitamin D supplementation had beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.
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