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Male fertility is improved in many ways by vitamin D – Jan 2014

Vitamin D and male reproduction

Nature Reviews Endocrinology 10, 175–186 (2014) doi:10.1038/nrendo.2013.262
Martin Blomberg Jensen, University Department of Growth and Reproduction, Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark.

VitaminDWiki

Vitamin D greatly improves Fertility

Increased male Vitamin D increases fertility

Decreased Fertility if decreased Vitamin D Receptor


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.

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References

  1. Sharpe, R. M., McKinnell, C., Kivlin, C. & Fisher, J. S. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125, 769–784 (2003). CASISIPubMedArticle
  2. Mortimer, D. et al. What should it take to describe a substance or product as 'sperm-safe'. Hum. Reprod. Update 19 (Suppl. 1), i1–i45 (2013).
  3. Bouillon, R. et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29, 726–776 (2008). CASISIPubMedArticle
  4. Blomberg Jensen, M. et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum. Reprod. 25, 1303–1311 (2010). CASPubMedArticle
  5. van Schoor, N. M. & Lips, P. Worldwide vitamin D status. Best Pract. Res. Clin. Endocrinol. Metab. 25, 671–680 (2011). CASPubMedArticle
  6. Holick, M. F. Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007). CASISIPubMedArticle
  7. Prosser, D. E. & Jones, G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29, 664–673 (2004). CASPubMedArticle
  8. Haussler, M. R., Jurutka, P. W., Mizwicki, M. & Norman, A. W. Vitamin D receptor (VDR)-mediated actions of 1α, 25(OH)2 vitamin D3: genomic and non-genomic mechanisms. Best Pract. Res. Clin. Endocrinol. Metab. 25, 543–559 (2011). CASPubMedArticle
  9. Verstuyf, A., Carmeliet, G., Bouillon, R. & Mathieu, C. Vitamin D: a pleiotropic hormone. Kidney Int. 78, 140–145 (2010). CASISIPubMedArticle
  10. Blomberg Jensen, M. & Dissing, S. Non-genomic effects of vitamin D in human spermatozoa. Steroids 77, 903–909 (2012). CASPubMedArticle
  11. Merke, J., Kreusser, W., Bier, B. & Ritz, E. Demonstration and characterisation of a testicular receptor for 1,25-dihydroxycholecalciferol in the rat. Eur. J. Biochem. 130, 303–308 (1983). CASPubMedArticle
  12. Johnson, J. A., Grande, J. P., Roche, P. C. & Kumar, R. Immunohistochemical detection and distribution of the 1,25-dihydroxyvitamin D3 receptor in rat reproductive tissues. Histochem. Cell Biol. 105, 7–15 (1996). CASISIPubMedArticle
  13. Mahmoudi, A. R. et al. Distribution of vitamin D receptor and 1α-hydroxylase in male mouse reproductive tract. Reprod. Sci. 20, 426–436 (2013). PUBMEDArticle
  14. Oliveira, A. G. et al. Vitamin D3 and androgen receptors in testis and epididymal region of roosters (Gallus domesticus) as affected by epididymal lithiasis. Anim. Reprod. Sci. 109, 343–355 (2008). CASPubMedArticle
  15. Schleicher, G., Privette, T. H. & Stumpf, W. E. Distribution of soltriol 1,25(OH)2-vitamin D3 binding sites in male sex organs of the mouse: an autoradiographic study. J. Histochem. Cytochem. 37, 1083–1086 (1989). CASPubMedArticle
  16. Corbett, S. T., Hill, O. & Nangia, A. K. Vitamin D receptor found in human sperm. Urology 68, 1345–1349 (2006). PUBMEDArticle
  17. Aquila, S. et al. Human sperm anatomy: ultrastructural localization of 1α, 25-dihydroxyvitamin D receptor and its possible role in the human male gamete. J. Anat. 213, 555–564 (2008). CASPubMedArticle
  18. Kidroni, G. et al. Vitamin D3 metabolites in rat epididymis: high 24,25-dihydroxy vitamin D3 levels in the cauda region. Biochem. Biophys. Res. Commun. 113, 982–989 (1983). CASPubMedArticle
  19. Erben, R. G. et al. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol. Endocrinol. 16, 1524–1537 (2002). CASISIPubMedArticle
  20. Gensure, R. C., Riggle, P. C., Antrobus, S. D. & Walters, M. R. Evidence for two classes of 1,25-dihydroxyvitamin D3 binding sites in classical vs. nonclassical target tissues. Biochem. Biophys. Res. Commun. 180, 867–873 (1991). CASPubMedArticle
  21. Aquila, S. et al. Human male gamete endocrinology: 1α, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism. Reprod. Biol. Endocrinol. 7, 140 (2009). CASPubMedArticle
  22. Blomberg Jensen, M. et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum. Reprod. 26, 1307–1317 (2011). CASPubMedArticle
  23. Blomberg Jensen, M. et al. Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo. Neoplasia 14, 952–963 (2012). PUBMED
  24. Zanatta, L., Bouraima-Lelong, H., Delalande, C., Silva, F. R. & Carreau, S. Regulation of aromatase expression by 1α, 25(OH)2 vitamin D3 in rat testicular cells. Reprod. Fertil. Dev. 23, 725–735 (2011). CASPubMedArticle
  25. Blomberg Jensen, M. et al. Characterization of the testicular, epididymal and endocrine phenotypes in the Leuven Vdr-deficient mouse model: targeting estrogen signalling. Mol. Cell Endocrinol. 377, 93–102 (2013). CASPubMedArticle
  26. Blomberg Jensen, M. et al. Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. Int. J. Androl 35, 499–510 (2012). CASPubMedArticle
  27. Oliva, R. Protamines and male infertility. Hum. Reprod. Update 12, 417–435 (2006). CASISIPubMedArticle
  28. Choudhary, D., Jansson, I., Stoilov, I., Sarfarazi, M. & Schenkman, J. B. Expression patterns of mouse and human CYP orthologs (families 1–4) during development and in different adult tissues. Arch. Biochem. Biophys. 436, 50–61 (2005). CASPubMedArticle
  29. Choudhary, D., Jansson, I., Schenkman, J. B., Sarfarazi, M. & Stoilov, I. Comparative expression profiling of 40 mouse cytochrome P450 genes in embryonic and adult tissues. Arch. Biochem. Biophys. 414, 91–100 (2003). CASPubMedArticle
  30. Foresta, C. et al. Bone mineral density and testicular failure: evidence for a role of vitamin D 25-hydroxylase in human testis. J. Clin. Endocrinol. Metab 96, E646–E652 (2011). CASISIPubMedArticle
  31. Olson, E. B. Jr, Knutson, J. C., Bhattacharyya, M. H. & DeLuca, H. F. The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3. J. Clin. Invest. 57, 1213–1220 (1976). CASPubMedArticle
  32. Addya, S., Zheng, Y. M., Shayiq, R. M., Fan, J. Y. & Avadhani, N. G. Characterization of a female-specific hepatic mitochondrial cytochrome P-450 whose steady-state level is modulated by testosterone. Biochemistry 30, 8323–8330 (1991). CASPubMedArticle
  33. Van, P. O., Argraves, W. S. & Morales, C. R. Co-expression and interaction of cubilin and megalin in the adult male rat reproductive system. Mol. Reprod. Dev. 64, 129–135 (2003). CASPubMedArticle
  34. Clulow, J., Jones, R. C. & Hansen, L. A. Micropuncture and cannulation studies of fluid composition and transport in the ductuli efferentes testis of the rat: comparisons with the homologous metanephric proximal tubule. Exp. Physiol. 79, 915–928 (1994). CASISIPubMed
  35. Cornwall, G. A. New insights into epididymal biology and function. Hum. Reprod. Update 15, 213–227 (2009). CASISIPubMedArticle
  36. Hess, R. A. et al. Estrogen and its receptors in efferent ductules and epididymis. J. Androl. 32, 600–613 (2011). CASPubMedArticle
  37. Weissgerber, P. et al. Male fertility depends on Ca2+ absorption by TRPV6 in epididymal epithelia. Sci. Signal. 4, ra27 (2011). CASPubMedArticle
  38. Huhtaniemi, I. & Toppari, J. Endocrine, paracrine and autocrine regulation of testicular steroidogenesis. Adv. Exp. Med. Biol. 377, 33–54 (1995). CASPubMed
  39. Costa, R. R., Reis, R. I., Aguiar, J. F. & Varanda, W. A. Luteinizing hormone (LH) acts through PKA and PKC to modulate T-type calcium currents and intracellular calcium transients in mice Leydig cells. Cell Calcium 49, 191–199 (2011). CASPubMedArticle
  40. Hochberg, Z. et al. Does 1,25-dihydroxyvitamin D participate in the regulation of hormone release from endocrine glands? J. Clin. Endocrinol. Metab 60, 57–61 (1985). CASPubMedArticle
  41. Zofková, I., Scholz, G. & Stárka, L. Effect of calcitonin and 1,25(OH)2-vitamin D3 on the FSH, LH and testosterone secretion at rest and LHRH stimulated secretion. Horm. Metab. Res. 21, 682–685 (1989). PUBMEDArticle
  42. Välimäki, V. V. et al. Serum estradiol, testosterone, and sex hormone-binding globulin as regulators of peak bone mass and bone turnover rate in young Finnish men. J. Clin. Endocrinol. Metab. 89, 3785–3789 (2004). CASISIPubMedArticle
  43. Ramlau-Hansen, C. H., Moeller, U. K., Bonde, J. P., Olsen, J. & Thulstrup, A. M. Are serum levels of vitamin D associated with semen quality? Results from a cross-sectional study in young healthy men. Fertil. Steril. 95, 1000–1004 (2011). CASPubMedArticle
  44. Hammoud, A. O. et al. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J. Androl. 14, 855–859 (2012). CASPubMedArticle
  45. Pilz, S. et al. Effect of vitamin D supplementation on testosterone levels in men. Horm. Metab. Res. 43, 223–225 (2011). CASPubMedArticle
  46. Wehr, E., Pilz, S., Boehm, B. O., Marz, W. & Obermayer-Pietsch, B. Association of vitamin D status with serum androgen levels in men. Clin. Endocrinol. (Oxf.) 73, 243–248 (2010). CASPubMedArticle
  47. Lee, D. M. et al. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur. J. Endocrinol. 166, 77–85 (2012). CASPubMedArticle
  48. Nimptsch, K., Platz, E. A., Willett, W. C. & Giovannucci, E. Association between plasma 25-OH vitamin D and testosterone levels in men. Clin. Endocrinol. (Oxf.) 77, 106–112 (2012). CASPubMedArticle
  49. Andersson, A. M., Carlsen, E., Petersen, J. H. & Skakkebaek, N. E. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period: possible effects of seasons. J. Clin. Endocrinol. Metab. 88, 932–937 (2003). CASPubMedArticle
  50. Chen, R. Y. et al. Relationship between calcium absorption and plasma dehydroepiandrosterone sulphate (DHEAS) in healthy males. Clin. Endocrinol. (Oxf.) 69, 864–869 (2008). CASPubMedArticle
  51. Sonnenberg, J., Luine, V. N., Krey, L. C. & Christakos, S. 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 118, 1433–1439 (1986). CASPubMedArticle
  52. Inpanbutr, N., Reiswig, J. D., Bacon, W. L., Slemons, R. D. & Iacopino, A. M. Effect of vitamin D on testicular CaBP28K expression and serum testosterone in chickens. Biol. Reprod. 54, 242–248 (1996). CASPubMedArticle
  53. Oury, F. et al. Endocrine regulation of male fertility by the skeleton. Cell 144, 796–809 (2011). CASISIPubMedArticle
  54. Pi, M. et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS ONE 3, e3858 (2008). CASADSPubMedArticle
  55. Johansen, J. S. et al. Serum bone Gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor I, and serum testosterone. J. Clin. Endocrinol. Metab. 67, 273–278 (1988). CASPubMedArticle
  56. Bolland, M. J., Grey, A., Horne, A. M. & Reid, I. R. Testosterone levels following decreases in serum osteocalcin. Calcif. Tissue Int. 93, 133–136 (2013). CASPubMedArticle
  57. Krishnan, A. V. et al. Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. Endocrinology 151, 32–42 (2010). CASISIPubMedArticle
  58. O'Donnell, L., Robertson, K. M., Jones, M. E. & Simpson, E. R. Estrogen and spermatogenesis. Endocr. Rev. 22, 289–318 (2001). CASISIPubMedArticle
  59. Hess, R. A. Estrogen in the adult male reproductive tract: a review. Reprod. Biol. Endocrinol. 1, 52 (2003). PUBMEDArticle
  60. Kinuta, K. et al. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 141, 1317–1324 (2000). CASPubMedArticle
  61. Bulun, S. E. et al. Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads. J. Clin. Endocrinol. Metab. 78, 1616–1621 (1994). CASPubMed
  62. Lanzino, M. et al. Aromatase messenger RNA is derived from the proximal promoter of the aromatase gene in Leydig, Sertoli, and germ cells of the rat testis. Biol. Reprod. 64, 1439–1443 (2001). CASPubMedArticle
  63. Carreau, S., Bourguiba, S., Lambard, S., Silandre, D. & Delalande, C. The promoter(s) of the aromatase gene in male testicular cells. Reprod. Biol. 4, 23–34 (2004). PUBMED
  64. Kato, S. et al. A calcium-deficient diet caused decreased bone mineral density and secondary elevation of estrogen in aged male rats—effect of menatetrenone and elcatonin. Metabolism 51, 1230–1234 (2002). CASPubMedArticle
  65. Hess, R. A. et al. A role for oestrogens in the male reproductive system. Nature 390, 509–512 (1997). CASADSISIPubMedArticle
  66. Joseph, A. et al. Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. Biol. Reprod. 82, 948–957 (2010). CASPubMedArticle
  67. Andersson, A. M., Petersen, J. H., Jorgensen, N., Jensen, T. K. & Skakkebaek, N. E. Serum inhibin B and follicle-stimulating hormone levels as tools in the evaluation of infertile men: significance of adequate reference values from proven fertile men. J. Clin. Endocrinol. Metab. 89, 2873–2879 (2004). CASPubMedArticle
  68. Dennis, N. A. et al. The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys. J. Clin. Endocrinol. Metab 97, 2450–2455 (2012). CASPubMedArticle
  69. Malloy, P. J., Peng, L., Wang, J. & Feldman, D. Interaction of the vitamin D receptor with a vitamin D response element in the Mullerian-inhibiting substance (MIS) promoter: regulation of MIS expression by calcitriol in prostate cancer cells. Endocrinology 150, 1580–1587 (2009). CASPubMedArticle
  70. Nef, S. & Parada, L. F. Cryptorchidism in mice mutant for Insl3. Nat. Genet. 22, 295–299 (1999). CASISIPubMedArticle
  71. Parikh, G. et al. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm. Metab. Res. 42, 754–757 (2010). CASADSPubMedArticle
  72. Skakkebaek, N. E., Giwercman, A. & de Kretser, D. Pathogenesis and management of male infertility. Lancet 343, 1473–1479 (1994). CASISIPubMedArticle
  73. Kwiecinski, G. G., Petrie, G. I. & DeLuca, H. F. Vitamin D is necessary for reproductive functions of the male rat. J. Nutr. 119, 741–744 (1989). CASPubMed
  74. Uhland, A. M., Kwiecinski, G. G. & DeLuca, H. F. Normalization of serum calcium restores fertility in vitamin D-deficient male rats. J. Nutr. 122, 1338–1344 (1992). CASPubMed
  75. Blomberg Jensen, M. Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction 144, 135–152 (2012). CASPubMedArticle
  76. Audet, I., Laforest, J. P., Martineau, G. P. & Matte, J. J. Effect of vitamin supplements on some aspects of performance, vitamin status, and semen quality in boars. J. Anim. Sci. 82, 626–633 (2004). CASPubMed
  77. Sood, S., Reghunandanan, R., Reghunandanan, V., Marya, R. K. & Singh, P. I. Effect of vitamin D repletion on testicular function in vitamin D-deficient rats. Ann. Nutr. Metab. 39, 95–98 (1995). CASPubMedArticle
  78. Hamden, K. et al. Inhibitory effects of 1α, 25dihydroxyvitamin D3 and Ajuga iva extract on oxidative stress, toxicity and hypo-fertility in diabetic rat testes. J. Physiol. Biochem. 64, 231–239 (2008). CASPubMedArticle
  79. Yang, B. et al. Associations between testosterone, bone mineral density, vitamin D and semen quality in fertile and infertile Chinese men. Int. J. Androl. 35, 783–792 (2012). CASPubMedArticle
  80. Naaby-Hansen, S. et al. Co-localization of the inositol 1,4,5-trisphosphate receptor and calreticulin in the equatorial segment and in membrane bounded vesicles in the cytoplasmic droplet of human spermatozoa. Mol. Hum. Reprod. 7, 923–933 (2001). CASPubMedArticle
  81. Norman, A. W. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am. J. Clin. Nutr. 88, 491S–499S (2008). CASISIPubMedArticle
  82. Blomberg Jensen, M. Active vitamin D or analogs thereof for use in in vivo or in vitro fertilization. Patent application (WO/2012/116699).
  83. Rojansky, N., Brzezinski, A. & Schenker, J. G. Seasonality in human reproduction: an update. Hum. Reprod. 7, 735–745 (1992). CASPubMed
  84. Chaganti, R. S. & Houldsworth, J. Genetics and biology of adult human male germ cell tumors. Cancer Res. 60, 1475–1482 (2000). CASISIPubMed
  85. Skakkebaek, N. E. Possible carcinoma-in-situ of the testis. Lancet 2, 516–517 (1972). CASISIPubMedArticle
  86. Sonne, S. B. et al. Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte. Cancer Res. 69, 5241–5250 (2009). CASPubMedArticle
  87. Kraggerud, S. M. et al. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis. Endocr. Rev. 34, 339–376 (2013). CASPubMedArticle
  88. Matusiak, D. & Benya, R. V. CYP27A1 and CYP24 expression as a function of malignant transformation in the colon. J. Histochem. Cytochem. 55, 1257–1264 (2007). CASPubMedArticle
  89. Blomberg Jensen M. et al. Expression of the vitamin D receptor, 25-hydroxylases, 1α-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer. J. Steroid Biochem. Mol. Biol. 121, 376–382 (2010). CASPubMedArticle
  90. Fleet, J. C. Molecular actions of vitamin D contributing to cancer prevention. Mol. Aspects Med. 29, 388–396 (2008). CASPubMedArticle
  91. De Jong, B. W. et al. Raman spectroscopic analysis identifies testicular microlithiasis as intratubular hydroxyapatite. J. Urol. 171, 92–96 (2004). CASISIPubMedArticle
  92. Holm, M., Lenz, S., De Meyts, E. R. & Skakkebaek, N. E. Microcalcifications and carcinoma in situ of the testis. BJU Int. 87, 144–149 (2001). CASPubMedArticle
  93. Jorgensen, A., Blomberg, J. M., Nielsen, J. E., Juul, A. & Rajpert-de, M. E. Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model. J. Steroid Biochem. Mol. Biol. 136, 238–246 (2013). CASPubMedArticle
  94. Koster, R. et al. Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer. J. Clin. Invest. 120, 3594–3605 (2010). CASPubMedArticle
  95. Feldman, D. R., Bosl, G. J., Sheinfeld, J. & Motzer, R. J. Medical treatment of advanced testicular cancer. JAMA 299, 672–684 (2008). CASISIPubMedArticle
  96. Nyomba, B. L., Bouillon, R. & De Moor, P. Evidence for an interaction of insulin and sex steroids in the regulation of vitamin D metabolism in the rat. J. Endocrinol. 115, 295–301 (1987). CASPubMedArticle
  97. Henry, H. L. Regulation of vitamin D metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 25, 531–541 (2011). CASPubMedArticle
  98. Chanakul, A. et al. FGF-23 regulates CYP27B1 transcription in the kidney and in extra-renal tissues. PLoS ONE 8, e72816 (2013). CASPubMedArticle
  99. Li, S. A. et al. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct. Funct. 29, 91–99 (2004). CASPubMedArticle
  100. Imai, M. et al. Klotho protein activates the PKC pathway in the kidney and testis and suppresses 25-hydroxyvitamin D3 1α-hydroxylase gene expression. Endocrine 25, 229–234 (2004). CASPubMedArticle
  101. Urakawa, I. et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770–774 (2006). CASADSISIPubMedArticle
  102. Razzaque, M. S. & Lanske, B. The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis. J. Endocrinol. 194, 1–10 (2007). CASISIPubMedArticle
  103. Steger, K., Tetens, F., Seitz, J., Grothe, C. & Bergmann, M. Localization of fibroblast growth factor 2 (FGF-2) protein and the receptors FGFR 1–4 in normal human seminiferous epithelium. Histochem. Cell Biol. 110, 57–62 (1998). CASPubMedArticle
  104. Lanske, B. & Razzaque, M. S. Premature aging in klotho mutant mice: cause or consequence? Ageing Res. Rev. 6, 73–79 (2007). PUBMEDArticle
  105. Usdin, T. B. et al. Tuberoinfundibular peptide of 39 residues is required for germ cell development. Endocrinology 149, 4292–4300 (2008). CASPubMedArticle
  106. Czykier, E., Zabel, M. & Surdyk-Zasada, J. Immunolocalization of PTHrP in prepubertal and pubertal testis of European bison. Folia Histochem. Cytobiol. 40, 373–375 (2002). PUBMED
  107. Pondel, M. Calcitonin and calcitonin receptors: bone and beyond. Int. J. Exp. Pathol. 81, 405–422 (2000). CASISIPubMedArticle
  108. Saarem, K. & Pedersen, J. I. Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5β-cholestane-3α, 7α, 12α-triol in female and male rat liver. Biochem. J. 251, 475–481 (1988). CASPubMed
  109. Saarem, K. & Pedersen, J. I. Sex differences in the hydroxylation of cholecalciferol and of 5β-cholestane-3α, 7α, 12α-triol in rat liver. Biochem. J. 247, 73–78 (1987). CASPubMed
  110. Small, M., Beastall, G. H., Semple, C. G., Cowan, R. A. & Forbes, C. D. Alteration of hormone levels in normal males given the anabolic steroid stanozolol. Clin. Endocrinol. (Oxf.) 21, 49–55 (1984). CASADSPubMedArticle
  111. Saunders, P. T. et al. Differential expression of oestrogen receptor α and β proteins in the testes and male reproductive system of human and non-human primates. Mol. Hum. Reprod. 7, 227–236 (2001). CASISIPubMedArticle
  112. Joseph, A., Shur, B. D. & Hess, R. A. Estrogen, efferent ductules, and the epididymis. Biol. Reprod. 84, 207–217 (2011). CASPubMedArticle
  113. Tanaka, Y., Castillo, L. & DeLuca, H. F. Control of renal vitamin D hydroxylases in birds by sex hormones. Proc. Natl Acad. Sci. USA 73, 2701–2705 (1976). CASADSPubMedArticle
  114. Nangia, A. K., Hill, O., Waterman, M. D., Schwender, C. E. & Memoli, V. Testicular maturation arrest to testis cancer: spectrum of expression of the vitamin D receptor and vitamin D treatment in vitro. J. Urol. 178, 1092–1096 (2007). CASPubMedArticle
  115. Kim, M. S. et al. DNA demethylation in hormone-induced transcriptional derepression. Nature 461, 1007–1012 (2009). CASISIPubMedArticle
  116. Chen, K. S. & DeLuca, H. F. Cloning of the human 1α,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements. Biochim. Biophys. Acta 1263, 1–9 (1995). PUBMEDArticle
  117. Gensure, R. C. et al. Homologous up-regulation of vitamin D receptors is tissue specific in the rat. J. Bone Miner. Res. 13, 454–463 (1998). CASPubMedArticle
  118. Muller, D. et al. Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1). Genomics 67, 48–53 (2000). CASISIPubMedArticle
  119. Schuh, K. et al. Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility. J. Biol. Chem. 279, 28220–28226 (2004). CASPubMedArticle
  120. Shiba, K. et al. Na+/Ca2+ exchanger modulates the flagellar wave pattern for the regulation of motility activation and chemotaxis in the ascidian spermatozoa. Cell Motil. Cytoskeleton 63, 623–632 (2006). CASPubMedArticle
  121. Corut, A. et al. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am. J. Hum. Genet. 79, 650–656 (2006). CASISIPubMedArticle
  122. Hinson, T. K. et al. Identification of putative transmembrane receptor sequences homologous to the calcium-sensing G-protein-coupled receptor. Genomics 45, 279–289 (1997). CASISIPubMedArticle
  123. Saini, R. K. et al. 1,25-dihydroxyvitamin D3 regulation of fibroblast growth factor-23 expression in bone cells: evidence for primary and secondary mechanisms modulated by leptin and interleukin-6. Calcif. Tissue Int. 92, 339–353 (2013). CASPubMedArticle
  124. Forster, R. E. et al. Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochem. Biophys. Res. Commun. 414, 557–562 (2011). CASPubMedArticle
  125. Shimasaki, S., Koba, A., Mercado, M., Shimonaka, M. & Ling, N. Complementary DNA structure of the high molecular weight rat insulin-like growth factor binding protein (IGF-BP3) and tissue distribution of its mRNA. Biochem. Biophys. Res. Commun. 165, 907–912 (1989). CASPubMedArticle
  126. Hirai, T. et al. Effect of 1,25-dihydroxyvitamin D on testicular morphology and gene expression in experimental cryptorchid mouse: testis specific cDNA microarray analysis and potential implication in male infertility. J. Urol. 181, 1487–1492 (2009). CASPubMedArticle
  127. Zanatta, L. et al. Effect of 1α, 25-dihydroxyvitamin D3 in plasma membrane targets in immature rat testis: ionic channels and gamma-glutamyl transpeptidase activity. Arch. Biochem. Biophys. 515, 46–53 (2011). CASPubMedArticle
  128. Rosso, A. et al. 1α, 25(OH)2-vitamin D3 stimulates rapid plasma membrane calcium influx via MAPK activation in immature rat Sertoli cells. Biochimie 94, 146–154 (2011). CASPubMedArticle
  129. Panda, D. K. et al. Targeted ablation of the 25-hydroxyvitamin D 1α-hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc. Natl Acad. Sci. USA 98, 7498–7503 (2001). CASADSPubMedArticle
  130. Oury F. et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J. Clin. Invest. 123, 2421–2433 (2013). CASPubMedArticle
  131. Jeong, J. H. et al. Expression of Runx2 transcription factor in non-skeletal tissues, sperm and brain. J. Cell Physiol. 217, 511–517 (2008). CASPubMedArticle


Martin Blomberg Jensen
Competing interests statement
The author declares that he holds two patent applications related to vitamin D and reproduction (patent WO/1016/17116 and WO/2012/116699).

Martin Blomberg Jensen studied medicine at the University of Copenhagen and obtained an MD degree in 2006. His interest in calcium and vitamin D signalling started during two clinical assignments at the department of Nephrology and Endocrinology, Rigshospitalet, Denmark. Since 2008, he has worked as an independent scientist under the supervision of Prof. Anders Juul in Department of Growth and Reproduction at Rigshospitalet, Denmark. His research has focused on the characterization of vitamin D signalling in male reproduction, which in part addresses the important relationship between bone signalling and gonadal function. The relationship between calcium homeostasis and male reproduction has not been characterized completely, and he is currently studying the role of selected vitamin D regulated genes and testicular regulators of vitamin D metabolism for male reproductive function.

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