Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates different aspects of human sperm biology and metabolism

Abstract

BackgroundA 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.Methods and ResultsBy 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.ConclusionOur 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.

Effects of 25OHD concentrations on chances of pregnancy and pregnancy outcomes: a cohort study in healthy Danish women

“…The vitamin D receptor is expressed in human sperm cells, and 1,25-dihydroxyvitamin D concentration may affect sperm survival and the acquisition of fertilizing ability of sperm cells. 3,4 Vitamin D status is assessed by measuring P-25OHD concentration 5 and is considered to be replete at P-25OHD concentrations 450 nmol/l, although recent studies have suggested that only P-25OHD 480 nmol/l should be considered as an optimal vitamin D status for non-skeletal outcomes. 6 P-25OHD insufficiency is widespread in all age groups, including younger women with childbearing potential.…”

Sperm metabolism in pig: a role for peroxisome proliferator-activated receptor (PPAR)γ

“…The effect of glucose on the fertilizing ability of sperm appears to be mediated by the pentose phosphate pathway (PPP) (Miraglia et al, 2010), and G6PDH is the key rate-limiting enzyme in this metabolic pathway, and has been shown to be functional in human spermatozoa (Aquila et al, 2009). As shown in Fig.7A, PGJ2 activates G6PDH activity at concentrations of 10 and 20mmoll -1…”

“…The conversion of NADP + to NADPH, catalyzed by G6PDH, was measured by the increase of absorbance at 340nm, as previously described (Aquila et al, 2005b;Aquila et al, 2006;Aquila et al, 2009).…”

“…Lipase activity was evaluated by the method of Panteghini et al (Panteghini et al, 2001) based on the use of DGGR [1,2-o-dilaurylrac-glycero-3-glutaric acid-(6Ј-methylresorufin) ester] as substrate, as previously described (Aquila et al, 2006;Aquila et al, 2009). …”

“…Triglycerides were measured in duplicate using a glycerol phosphate oxidase-peroxidase enzymatic colorimetric method according to the manufacturer's instructions (Biogemina Italia, Catania, Italy) in sperm lysates and as previously described (Aquila et al, 2006;Aquila et al, 2009). Data are presented as mg10 -9 sperm.…”