University Department of Growth and Reproduction, Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Nat Rev Endocrinol. 2014 Mar;10(3):175-86. doi: 10.1038/nrendo.2013.262. Epub 2014 Jan 14.
Vitamin D is a versatile signalling molecule with a well-established role in the regulation of calcium homeostasis and bone health. The spectrum of vitamin D target organs has expanded and the reproductive role of vitamin D is highlighted by expression of the vitamin D receptor (VDR) and enzymes that metabolize vitamin D in testis, male reproductive tract and human spermatozoa. The expression levels of VDR and CYP24A1 in human spermatozoa serve as positive predictive markers of semen quality, and VDR mediates a nongenomic increase in intracellular calcium concentration that induces sperm motility. Interestingly, functional animal models show that vitamin D is important for estrogen signalling and sperm motility, while cross-sectional studies support the positive association between serum 25-hydroxyvitamin D level and sperm motility in both fertile and infertile men. Expression of VDR and enzymes that metabolize vitamin D in fetal testis indicates a yet unknown role during development, which may be extrapolated from invasive testicular germ cell tumours where 1α,25-dihydroxyvitamin D induces a mesodermal differentiation of the pluripotent testicular cancer cells. Taken together, vitamin D signalling has a positive effect on semen quality, increases estrogen responsiveness and differentiates germ cell tumours. Future studies are needed to determine when 1α,25-dihydroxyvitamin D acts in a paracrine manner and whether systemic changes, which are subject to pharmacological modulation, could influence male reproductive function.
维生素 D 是一种多功能信号分子,在钙稳态和骨骼健康的调节中具有明确的作用。维生素 D 的靶器官范围已经扩大,维生素 D 受体 (VDR) 和代谢维生素 D 的酶在睾丸、男性生殖道和人类精子中的表达突出了其生殖作用。VDR 和 CYP24A1 在人类精子中的表达水平可作为精液质量的阳性预测标志物,VDR 介导细胞内钙浓度的非基因组增加,从而诱导精子运动。有趣的是,功能动物模型表明维生素 D 对雌激素信号和精子运动很重要,而横断面研究支持血清 25-羟维生素 D 水平与生育力和不育男性精子运动之间的正相关。VDR 和代谢维生素 D 的酶在胎儿睾丸中的表达表明其在发育过程中具有未知的作用,这可能从侵袭性睾丸生殖细胞肿瘤中推断出来,其中 1α,25-二羟维生素 D 诱导多能睾丸癌细胞的中胚层分化。总之,维生素 D 信号对精液质量有积极影响,增加雌激素反应性,并分化生殖细胞瘤。需要进一步的研究来确定 1α,25-二羟维生素 D 何时以旁分泌方式起作用,以及是否可以通过药理学调节来影响男性生殖功能的系统性变化。