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The role of vitamin D in male fertility: A focus on the testis

Abstract

In the last decade, vitamin D has emerged as a pleiotropic molecule with a multitude of autocrine, paracrine and endocrine functions, mediated by classical genomic as well as non-classical non-genomic actions, on multiple target organs and systems. The expression of vitamin D receptor and vitamin D metabolizing enzymes in male reproductive system, particularly in the testis, suggests the occurrence of vitamin D synthesis and regulation as well as function in the testis. The role of vitamin D in the modulation of testis functions, including hormone production and spermatogenesis, has been investigated in animals and humans. Experimental studies support a beneficial effect of vitamin D on male fertility, by modulating hormone production through genomic and non-genomic actions, and, particularly, by improving semen quality essentially through non-genomic actions. However, clinical studies in humans are controversial. Indeed, vitamin D seems to contribute to the modulation of the bioavailable rather than total testosterone. Moreover, although an increased prevalence or risk for testosterone deficiency was reported in men with vitamin D deficiency in observational studies, the majority of interventional studies demonstrated the lack of effect of vitamin D supplementation on circulating levels of testosterone. The most consistent effect of vitamin D was reported on semen quality. Indeed, vitamin D was shown to be positively associated to sperm motility, and to exert direct actions on spermatozoa, including non-genomic driven modulation of intracellular calcium homeostasis and activation of molecular pathways involved in sperm motility, capacitation and acrosome reaction. The current review provides a summary of current knowledge on the role of vitamin D in male fertility, by reporting clinical and experimental studies in humans and animals addressing the relationship between vitamin D and testis function.

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CdA and MG conceived and developed the manuscript in all its aspects, performed the literature search, wrote the manuscript, conceived and prepared tables and figs. CP substantially contributed to the writing of the section on the expression of VDR and VitD metabolizing enzymes in the male reproductive system. FG, DM and CS substantially contributed to the writing of the sections on clinical studies. GG substantially contributed to the writing of the sections on the relationship between VitD and semen quality. AV substantially contributed to the preparation of tables and figs. AC critically reviewed and revised the manuscript. RP is the principal investigator, helped conceive and supervised the manuscript drafting, critically reviewed and revised it for important intellectual content. FC was added as author in the revised version of the manuscript since she provided a significant contribution to the scientific content of the manuscript during the revision process; in particular, she substantially contributed to the writing of the section on testis function. MP was added as author in the revised version of the manuscript since she provided a significant contribution to the graphic content of the manuscript during the revision process; in particular, she substantially contributed to schematization of data and to the preparation of tables and figures. All authors, including those listed on the first submitted version of the manuscript and those added to the revised version, read and approved the final manuscript. All authors, including those listed on the first submitted version of the manuscript and those added to the revised version, agree to the proposed new authorship.

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Correspondence to Rosario Pivonello.

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Cristina de Angelis and Mariano Galdiero equally contributed to the manuscript

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de Angelis, C., Galdiero, M., Pivonello, C. et al. The role of vitamin D in male fertility: A focus on the testis. Rev Endocr Metab Disord 18, 285–305 (2017). https://doi.org/10.1007/s11154-017-9425-0

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Keywords

  • Vitamin D
  • Male fertility
  • Testis
  • Hormone production
  • Testosterone
  • Semen quality
  • Environment
  • Lifestyle