TY - JOUR
T1 - Non-genomic effects of vitamin D in human spermatozoa
AU - Blomberg Jensen, Martin
AU - Dissing, Steen
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - 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 [Ca 2+]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.
AB - 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 [Ca 2+]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.
U2 - 10.1016/j.steroids.2012.02.020
DO - 10.1016/j.steroids.2012.02.020
M3 - Journal article
C2 - 22414629
SN - 0370-7466
VL - 77
SP - 903
EP - 909
JO - Research on Steroids
JF - Research on Steroids
IS - 10
ER -