The role of vitamin D in male fertility, A focus on the testis – Sept 2017

Rev Endocr Metab Disord. 2017 Sep;18(3):285-305. doi: 10.1007/s11154-017-9425-0.
de Angelis C1, Galdiero M1, Pivonello C2, Garifalos F2, Menafra D2, Cariati F3,4, Salzano C2, Galdiero G2, Piscopo M2, Vece A2, Colao A2, Pivonello R5.
1 I.O.S. & COLEMAN Srl, Naples, Italy.
2 Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Naples, Italy.
3 CEINGE Biotecnologie Avanzate s.c.a r.l., Naples, Italy.
4 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università "Federico II" di Napoli, Naples, Italy.
5 Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Naples, Italy. rosario.pivonello@unina.it.

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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.

Table 5 Summary of Clinical Observational and Interventional Studies - Relationship Between Vitamin D and Semen Quality

↑, increase or positive association    decrease or negative association   =, no change or no association;

• *Subjects referring for fertility issues.
• Abbreviations: OBS, observational study; INT, interventional study; T, total motility; P, progressive motility; Na, Not available; NA, Not Assessed.
• 1, Adjusted for: season, diseases of reproductive organs, smoking, maternal smoking or alcohol intake during pregnancy, abstinence, spillage during semen collection, time from collection;
• 2, Adjusted for: age, BMI, season, alcohol intake and smoking;
• 3, Adjusted for: age, BMI, smoking, season, abstinence, time from collection, free testosterone and estradiol, total estradiol, testosterone/estradiol ratio, SHBG;
• 4, Adjusted for: season, medications, fever, abstinence, serum calcium, FSH;
• 5, Adjusted for: season, abstinence, time from collection;
• 6, Adjusted for: age, BMI, varicocele, total testosterone;
• 7, Adjusted for: age, BMI, season;
• 8, comp