Vitamin-D Deficiency and Male Reproduction

Special Article - Vitamin D Deficiency

Ann Nutr Disord & Ther. 2016; 3(2): 1035.

Vitamin-D Deficiency and Male Reproduction

Taglianetti S, De Rocco Ponce M, Ghezzi M and Foresta C*

Department of Medicine, University of Padova, Italy

*Corresponding author: Foresta C, Department of Medicine, University of Padova, Unit of Andrology and Reproductive Medicine, Via Giustiniani, 2, 35128 Padova, Italy

Received: November 15, 2016; Accepted: December 22, 2016; Published: December 26, 2016


Purpose: Vitamin D (VD) can be considered a functional steroid hormone with a well-established effect on musculoskeletal health. The purpose of this systematic review was to investigate the role of vitamin D in male reproduction, presenting current evidence from experimental animal and human studies. The basis of this interplay lays on the presence of Vitamin D-Receptor (VDR) and Vitamin D (VD) metabolizing enzymes in testis and male reproductive tract.

Methods: Using PubMed, we searched for publications during the last 30 years that investigated the role of vitamin D in male reproduction.

Results: Evidence from animal and human studies suggests a possible role of vitamin D in male reproduction. Epidemiological studies suggest a positive association between 25-hydroxy-vitamin D [25(OH)D] and semen parameters and androgen levels. On the other hand, several studies reported that high vitamin D levels may have a negative effect on gonadal function.

Conclusions: Further large prospective studies are warranted to prove a casual relationship between vitamin D and male reproduction and the impact of vitamin D supplementation on gonadal function.

Keywords: Vitamin D; Androgens; Fertility; Male reproduction; Sperm; Supplementation


1a,25(OH)2D3: 1alpha,25-Dihydroxyvitamin D3; BMD: Bone Mineral Density; BMI: Body Mass Index; CYP24A1: 24R-Hydroxylase; CYP27B1: 1a-Hydroxylase; CYP2R1: 25-Hydroxylase; FSH: Follicle Stimulating Hormone; GPRC6A: G-Protein Coupled Receptor Family C Group 6 Member A; HCG: Human Chorionic Gonadotropin; INSL3: Insulin-Like 3; LH: Luteinizing Hormone; OC: Osteocalcin; 25(OH)D: 25-Hydroxyvitamin D; PKA: Protein Kinase A; PKC: Protein Kinase C; RXR: Retinoid X Receptor; SHBG: Sex Hormone- Bindng Globuline; SOCE: Store-Operated Calcium Entry; TRPV6: Transient Receptor Potential Cation Channel Subfamily V Member 6; ucOC: uncarboxylated-OC; VD: Vitamin D; VDR: Vitamin D Receptor; VDREs: Vitamin D-Responsive Elements.


Vitamin D (VD) is a versatile signaling molecule that could be properly considered a functional steroid hormone. Currently, there is great interest in VD for its possible “non-classical” effects in addition to the well-known role on bone metabolism, especially on male gonadal function [1,2].

Vitamin D synthesis and role

In humans the VD status is mainly determined by ultraviolet-B radiation of the skin, while VD intake by nutrition and supplements plays only a minor role [3].

Thereafter, VD is hydroxylated at the C25 position of the side chain. This hydroxylation takes place in the liver and other tissues such as testes by 25-hydroxylase (identified as CYP2R1 or CYP27A1). The product of this reaction is 25-hydroxyvitamin D [25(OH) D], which is commonly used to evaluate VD levels. 1alpha,25- dihydroxyvitamin D3 [1a,25(OH)2D3], is the active metabolite obtained by 1a-hydroxylase (CYP27B1) from 25(OH)D in the kidneys, as well as in other tissues including human testis [4].

The broad biological actions of VD which involve the regulation of about 3% of the human genome are mediated through the Vitamin D Receptor (VDR) [1].

The VDR acts as a transcription factor binding to Vitamin D Responsive Elements (VDREs) in the promoter region of target genes after forming a VDR-RXR heterocomplex with the Retinoid X Receptor (RXR) [5]. The VDR is almost ubiquitously expressed in human cells, suggesting an endocrine role of the VD [3,6,7]. In the kidney, 25(OH)D and 1a,25(OH)2D3 are catabolized by 24R-hydroxylase (identified as CYP24A1) to 24R,25(OH)2D3 and 1-a 24R,25(OH)3D3, respectively [8] (Figure 1).