Aquila S, Guido C, Middea E, et al.. Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism. Reprod Biol Endocrinol.7:140

Dept Pharmaco-Biology, University of Calabria 87036 Arcavacata di Rende, Cosenza, Italy.
Reproductive Biology and Endocrinology (Impact Factor: 2.23). 11/2009; 7(1):140. DOI: 10.1186/1477-7827-7-140
Source: PubMed


A wider biological role of 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D3, in tissues not primarily related to mineral metabolism was suggested. Recently, we evidenced the ultrastructural localization the 1,25(OH)2D3 receptor in the human sperm. However, the 1,25(OH)2D3 action in human male reproduction has not yet been clarified.
By RT-PCR, Western blot and Immunofluorescence techniques, we demonstrated that human sperm expresses the 1,25(OH)2D3 receptor (VDR). Besides, 25(OH)D3-1 alpha-hydroxylase, evidenced by Western blot analysis, indicated that in sperm 1,25(OH)2D3 is locally produced, highlighting the potential for autocrine-paracrine responses. 1,25(OH)2D3 through VDR, increased intracellular Ca2+ levels, motility and acrosin activity revealing an unexpected significance of this hormone in the acquisition of fertilizing ability. In sperm, 1,25(OH)2D3 through VDR, reduces triglycerides content concomitantly to the increase of lipase activity. Rapid responses stimulated by 1,25(OH)2D3 have been observed on Akt, MAPK and GSK3 implying that this secosteroid is involved in different sperm signalling pathways.
Our data extended the role of 1,25(OH)2D3 beyond its conventional physiological actions, paving the way for novel therapeutic opportunities in the treatment of the male reproduction disorders.

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Available from: Rosalinda Bruno, Oct 04, 2015
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    • "Vitamin D may play a role in human spermatogenesis. The favourable effect of 25(OH) on human spermatozoa has been shown in vitro[26-28] and three cross-sectional association studies on serum 25(OH)D levels and semen quality have been conducted in young healthy men without infertility problems [27,29,30]. The results, however, were quite discordant (Table 1). "
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    ABSTRACT: Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the human reproductive system in both genders, but no comprehensive analysis of the potential relationship between vitamin D status and Assisted Reproduction Technologies (ART) outcomes is currently available. On this basis, the purpose of this systematic review and meta-analysis was to perform an in-depth evaluation of clinical studies assessing whether vitamin D status of patients undergoing ART could be related to cycle outcome variables. This issue is of interest considering that vitamin D deficiency is easily amenable to correction and oral vitamin D supplementation is cheap and without significant side effects. Surprisingly, no studies are currently available assessing vitamin D status among male partners of couples undergoing ART, while seven studies on vitamin D status of women undergoing controlled ovarian hyperstimulation (COH) for ART were found and included in the review. Results show that vitamin D deficiency is highly prevalent among women undergoing COH, ranging from 21% to 31% across studies conducted in Western countries and reaching 75-99% in Iranian studies. Data on vitamin D deficiency (25-hydroxyvitamin D serum levels <20 ng/ml) in relation to ART outcomes could be extracted from three studies and included in the meta-analysis, yielding a common risk ratio (RR) of 0.89 (95% CI 0.53-1.49) and showing a lower but not statistically significant likelihood of clinical pregnancy for vitamin-D-deficient women compared with vitamin-D-sufficient patients. In conclusion, there is insufficient evidence to support the routine assessment of vitamin D status to predict the clinical pregnancy rate in couples undergoing ART. The partly conflicting results of the available studies, potentially explaining the lack of statistical significance for a negative influence of vitamin D deficiency on clinical pregnancy rate, are likely secondary to confounders and insufficient sample size, and further larger cohort and randomised controlled studies are required.
    Reproductive Biology and Endocrinology 05/2014; 12(1):47. DOI:10.1186/1477-7827-12-47 · 2.23 Impact Factor
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    • "An activity of 1 α-hydroxylase in spermatozoa cells points a local synthesis of vitamin D and its autocrine and paracrine activity (Fig. 1). 1,25[OH] 2 D increases an intracellular concentration of Ca +2 ions, and affects an activity of acrosine, one of the enzymes involved in acrosome reaction (Aquila et al., 2009). However, despite a high number of fundamental research, the available data concerning biological effect of vitamin D on fertility are very poor and often unequivocal. "
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    ABSTRACT: Vitamin D is currently in the scope of research in many fields of medicine. Despite that its influence on health remains uncertain. This paper presents the review of the publications concerning the role of calciferol in reproduction processes and its significance in infertility therapy covering topics of polycystic ovary syndrome, endometriosis infertility, myoma infertility, male infertility, premature ovary failure and in vitro fertilization techniques. The results of latest research articles in those fields has been discussed and summarized. The deficiency of vitamin defined as the concentration of 25-hydroxycalciferol <20 ng/ml is frequently noted in patients of fertility clinics. Serum vitamin D concentration in healthy women is higher comparing to PCOS patients. The supplementation with vitamin D should be applied in the schemes of PCOS treatment both due to an improved insulin resistance and the results of infertility treatment. The explanation of vitamin D activity mechanism in patients with PCOS requires further research. Vitamin D have direct effect on AMH production, and thus increase longer maintenance of ovarian reserve in the patients with its higher concentration. The occurrence of uterine myomas in the group with vitamin D deficiency was evaluated as much higher comparing to controls. On the other hand it is supposed that high concentration of calciferol may be related to an impaired elimination of endometrial cells passing to peritoneal cavity via ovarian reflux causing endometriosis. In male infertility both low (<20 ng/ml) and high (>50 ng/ml) concentration of vitamin D in serum negatively affects spermatozoa number per ml of semen, their progressive movement and morphology. Significant differences as a response on ovulation stimulation, number and quality of embryos depending on vitamin D concentration were not observed in none of the analyzed papers concerning the role of vitamin D in in vitro fertilization (IVF). Better results in patients without calciferol insufficiency are explained by reports about high concentration of vitamin D and its metabolites in human in decidua collected in the 1st trimester of pregnancy which suggests its contribution in proper implantation and local immunological preference of the embryo. It is accepted that the treatment requires vitamin D concentration below 20 ng/ml (up to 50 nmol/l), especially in obese women, these with insulin resistance and small ovarian reserve and in men with oligo- and asthenozoospermia.
    Neuro endocrinology letters 12/2013; 34(8):756-62. · 0.80 Impact Factor
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    • "Since spermatozoa are transcriptionally silent, and are affected by both calcium channel blockers and calcium, we speculated (supported by seven references) that vitamin D increases intracellular calcium in mature spermatozoa. Our suggestion has now been further supported by a recent study published by Aquila et al. (2009). Thus, it seems appropriate to speculate that vitamin D affects the calcium levels in spermatozoa. "
    Human Reproduction 08/2010; 25(8):2152-3; author reply 2153. DOI:10.1093/humrep/deq114 · 4.57 Impact Factor
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