Selection of High-Quality Spermatozoa May Be Promoted by Activated Vitamin D in the Woman

Context: The vitamin D receptor (VDR) and enzymes involved in activation (CYP2R1, CYP27B1) and inactivation (CYP24A1) of vitamin D are expressed in ovary, testes, and spermatozoa. Objective: Determine responsiveness to 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] in spermatozoa from normal and infertile men, and identify the site of exposure and how 1,25(OH)(2)D-3 influences sperm function. Design: Spermatozoa expressing VDR, CYP2R1, CYP27B1, and CYP24A1 were analyzed in normal and infertile men. 25-Hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)(2)D-3], and 1,25(OH)(2)D-3 were measured in serum, seminal fluid, cervical secretions, and ovarian follicular fluid. 1,25(OH) 2D3 was tested on human spermatozoa. Setting: Tertiary center for fertility. Participants: Protein expression in spermatozoa and semen quality were assessed in 230 infertile and 114 healthy men. Vitamin D metabolites were measured in fluids from 245 men and 13 women, while 74 oocytes and 17 semen donors were used for sperm-function tests. Main Outcome Measures: VDR and CYP24A1 expressions in spermatozoa, fluid concentrations of 25-OHD, 24,25(OH)(2)D-3, and 1,25(OH)(2)D-3, and 1,25(OH)(2)D-3-induced effects on intracellular calcium concentration ([Ca2+](i)) and sperm-oocyte binding in vitro. Results: VDR and CYP24A1 were expressed in a >2-fold higher fraction of spermatozoa from normal than infertile men (P, 0.01). Concentrations of 25-OHD, 24,25(OH)(2)D, and 1,25(OH)(2)D-3 were undetectable in seminal fluid but high in ovarian follicular fluid. Follicular concentrations of 1,25(OH)(2)D-3 induced a modest increase in [Ca2+] i and sperm-oocyte binding in vitro (P,0.05). Conclusion: Presence of VDR and CYP24A1 mainly in spermatozoa of higher quality supports that 1,25(OH)(2)D-3 available in the female reproductive tract may promote selection of the best gametes for fertilization.