Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality

TY - JOUR

T1 - Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality

AU - Jensen, Martin Blomberg

AU - Jørgensen, A

AU - Nielsen, J E

AU - Bjerrum, P J

AU - Skalkam, M

AU - Petersen, J H

AU - Egeberg, D L

AU - Bangsbøll, S

AU - Andersen, A N

AU - Skakkebaek, N E

AU - Juul, A

AU - Rajpert-De Meyts, E

AU - Dissing, S

AU - Leffers, H

AU - Jørgensen, N

N1 - © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

PY - 2012/8

Y1 - 2012/8

N2 - Vitamin D (VD) is important for male reproduction in mammals and the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD-inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is transcriptionally regulated by VD, and has a distinct expression at the sperm annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1. Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of 1,25(OH)(2) D(3) on intracellular calcium concentration ([Ca(2+) ](i) ) and sperm motility. Double ICC staining showed that CYP24A1 and VDR were either concomitantly expressed or absent in 80% of the spermatozoa from young men. The median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus significantly (p 3% CYP24A1-positive spermatozoa distinguished young men from subfertile men with a sensitivity of 66.0%, a specificity of 77.9% and a positive predictive value of 98.3%. Functional studies revealed that 1,25(OH)(2) D(3) increased [Ca(2+) ](i) and sperm motility in young healthy men, while 1,25(OH)(2) D(3) was unable to increase motility in subfertile patients. In conclusion, we suggest that CYP24A1 expression at the annulus may serve as a novel marker of semen quality and an objective proxy for sperm function.

AB - Vitamin D (VD) is important for male reproduction in mammals and the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD-inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is transcriptionally regulated by VD, and has a distinct expression at the sperm annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1. Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of 1,25(OH)(2) D(3) on intracellular calcium concentration ([Ca(2+) ](i) ) and sperm motility. Double ICC staining showed that CYP24A1 and VDR were either concomitantly expressed or absent in 80% of the spermatozoa from young men. The median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus significantly (p 3% CYP24A1-positive spermatozoa distinguished young men from subfertile men with a sensitivity of 66.0%, a specificity of 77.9% and a positive predictive value of 98.3%. Functional studies revealed that 1,25(OH)(2) D(3) increased [Ca(2+) ](i) and sperm motility in young healthy men, while 1,25(OH)(2) D(3) was unable to increase motility in subfertile patients. In conclusion, we suggest that CYP24A1 expression at the annulus may serve as a novel marker of semen quality and an objective proxy for sperm function.

U2 - 10.1111/j.1365-2605.2012.01256.x

DO - 10.1111/j.1365-2605.2012.01256.x

M3 - Journal article

C2 - 22404291

SN - 0105-6263

VL - 35

SP - 499

EP - 510

JO - International Journal of Andrology

JF - International Journal of Andrology

IS - 4

ER -