University Department of Growth and Reproduction GR, Rigshospitalet section 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Hum Reprod. 2010 May;25(5):1303-11. doi: 10.1093/humrep/deq024. Epub 2010 Feb 18.
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.
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.
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.
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.
维生素 D 受体 (VDR) 在人睾丸中表达,维生素 D (VD) 被认为影响成熟精子的存活和功能。事实上,VDR 敲除小鼠和 VD 缺乏大鼠的精子计数减少,生育率低。然而,VD 的细胞反应很复杂,因为它不仅依赖于 VDR 的表达,还依赖于循环 VD 的细胞摄取以及 VD 代谢酶的存在和活性。VD 代谢酶在人睾丸和男性生殖道中的表达以前尚未被研究过。因此,我们对睾丸、附睾、精囊 (SV)、前列腺和精子中 VDR、VD 激活 (CYP2R1、CYP27A1、CYP27B1) 和失活 (CYP24A1) 酶的表达进行了全面分析。
经睾丸切除术 (睾丸 n = 13;附睾 n = 7)、前列腺切除术 (前列腺 n = 5 和 SVs n = 3) 获得组织样本,并从精液中获得样本 (n = 13)。使用 RT-PCR 检测 mRNA,并用免疫组织化学法检测蛋白质的表达。
VDR 和 VD 代谢酶在圆形和长形精子、附睾头部的小泡以及附睾尾部、SV 和前列腺的腺上皮中同时表达。射出精子的表达模式不同,尽管在成熟精子的亚群中观察到 VDR、CYP2R1、CYP27B1 和 CYP24A1 在颈部和中段的同时表达。
基于 VDR 和 VD 代谢酶在人睾丸、射精管和成熟精子中的显著表达,我们认为 VD 对人类精子的发生和成熟很重要。