Non-genomic effects of vitamin D in human spermatozoa

• Published in: Steroids Vol. 77; no. 10; pp. 903 - 909
• Main Authors: Blomberg Jensen, Martin, Dissing, Steen
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.08.2012; Elsevier
• Subjects: Acrosome Reaction; Animals; Biological and medical sciences; Calcium; Calcium Signaling; CatSper; CYP24A1; Fundamental and applied biological sciences. Psychology; Genome, Human; Humans; Kinetics; Male; Progesterone; Progesterone - physiology; Rapid effects; Receptors, Calcitriol - metabolism; Spermatozoa - metabolism; Steroid receptor; Vertebrates: endocrinology; Vitamin D - physiology; Rapid effects; Steroid receptor; CatSper; CYP24A1; Progesterone; Calcium; Human; Steroid; Spermatozoa; Germinal cell; Inorganic element; Ovarian hormone; Progestagen; Micronutrient; Vitamin D; Sex steroid hormone; Biological receptor
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2012.02.020

[Display omitted] ► 1,25(OH)2D3 increases intracellular calcium concentration [Ca2+]i in human spermatozoa. ► VDR mediates rapid Ca2+-release through the alternative VDR binding pocket. ► The rise in [Ca2+]i originates from Ca2+-release of intracellular stores. ► 1,25(OH)2D3 induce sperm motility and the acrosome reaction in vitro. ► The vitamin D response differs from the progesterone mediated Ca2+-rise. The spectrum for vitamin D (VD) mediated effects has expanded in recent years. Activated VD (1,25(OH)2D3) binds to the VD receptor (VDR) and mediates non-genomic effects through the alternative ligand binding-pocket (VDR-ap) or regulates gene transcription through the genomic binding-pocket. VDR and VD-metabolizing enzymes are expressed in human testis, male reproductive tract and mature spermatozoa, and VD is considered important for male reproduction. Expression of the VD-inactivating enzyme CYP24A1 at the annulus of human spermatozoa distinguish normal and infertile men with high specificity, and CYP24A1 expression is positively correlated with all semen variables and suggested as a marker for both semen quality and VD responsiveness. Moreover, spermatozoa are transcriptionally silent and are therefore a unique model to study non-genomic effects. 1,25(OH)2D3 induced a rapid increase in intracellular calcium concentration [Ca2+]i in human spermatozoa. The [Ca2+]i increase was abrogated by the non-genomic VDR antagonist 1β,25(OH)2D3, while the specific agonist for VDR-ap (JN) increased [Ca2+]i with similar kinetics as 1,25(OH)2D3. The rise in [Ca2+]i originated as a Ca2+-release from intracellular stores since inhibition of phospholipase-C diminished the 1,25(OH)2D3 mediated Ca2+ response, while suspending spermatozoa in a nominally Ca2+-free medium did not affect the VD mediated Ca2+ rise. The spatio-temporal kinetics of the VD-response differed from the progesterone-mediated increase in [Ca2+]i as the VD-mediated Ca2+ rise was not observed in the tail region and was independent of extracellular Ca2+. A functional role of the VD-mediated Ca2+ increase was supported by showing that 1,25(OH)2D3 increased sperm motility and induced the acrosome reaction in vitro.