Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract.
BACKGROUND
The vitamin D receptor (VDR) is expressed in human testis, and vitamin D (VD) has been suggested to affect survival and function of mature spermatozoa. Indeed, VDR knockout mice and VD deficient rats show decreased sperm counts and low fertility. However, the cellular response to VD is complex, since it is not solely dependent on VDR expression, but also on cellular uptake of circulating VD and presence and activity of VD metabolizing enzymes. Expression of VD metabolizing enzymes has not previously been investigated in human testis and male reproductive tract. Therefore, we performed a comprehensive analysis of the expression of VDR, VD activating (CYP2R1, CYP27A1, CYP27B1) and inactivating (CYP24A1) enzymes in the testis, epididymis, seminal vesicle (SV), prostate and spermatozoa.


METHODS
Tissue samples were obtained after orchiectomy (testis n = 13; epididymis n = 7), prostatectomy (prostate n = 5 and SVs n = 3) and semen samples obtained after ejaculation (n = 13). mRNA was detected with RT-PCR and expression of proteins was determined by immunohistochemistry.


RESULTS
VDR and VD metabolizing enzymes were concomitantly expressed in round and elongated spermatids, vesicles within the caput epididymis, and glandular epithelium of cauda epididymis, SV and prostate. The expression pattern in ejaculated spermatozoa varied, although, concomitant expression of VDR, CYP2R1, CYP27B1 and CYP24A1 was observed in neck and midpiece in a subpopulation of mature spermatozoa.


CONCLUSIONS
On the basis of the marked expression of VDR and the VD metabolizing enzymes in human testis, ejaculatory tract and mature spermatozoa, we suggest that VD is important for spermatogenesis and maturation of human spermatozoa.
Blomberg Jensen
Martin
M
University Department of Growth and Reproduction GR, Rigshospitalet section 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. mabj@rh.regionh.dk
Nielsen
John E
JE
Jørgensen
Anne
A
Rajpert-De Meyts
Ewa
E
Kristensen
David Møbjerg
DM
Jørgensen
Niels
N
Skakkebaek
Niels E
NE
Juul
Anders
A
Leffers
Henrik
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001483:Base Sequence; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D017931:DNA Primers / Q000235:genetics; D004822:Epididymis / Q000378:metabolism; D015870:Gene Expression; D005837:Genitalia, Male / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011467:Prostate / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012669:Seminal Vesicles / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D017931:DNA Primers; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; C585550:Cyp24a1 protein, mouse; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase