Infertility, Female Clinical Trial
Official title:
Plasma Concentrations of Calcium, Phosphate, FGF23, Klotho, 25 (OH) D3 and 1,25 (OH) 2D3 From Patients Who Wants to Have Children
1,25-dihydroxy-vitamin D3 (1,25 (OH) 2D3) or calcitriol regulates plasma calcium and phosphate concentrations in the blood by stimulating intestinal absorption and renal reabsorption of calcium and phosphate. 1.25 (OH) 2D3 is formed by the renal 1α25OH vitamin D-hydroxylase (Cyp27b1) and inactivated by the renal 25-hydroxy vitamin D-24-hydroxylase (Cyp24). Unpublished studies in mice revealed an inhibitory effect of 1.25 (OH) 2D3 on embryo implanation. An excess of 1.25 (OH) 2D3 could therefore lead to female infertility. The excess of 1.25 (OH) 2D3 could result from uncritical vitamin D intake with insufficient negative feedback by FGF23 / Klotho. The aim of the study is to identify patients with an excess of 1.25 (OH) 2D3.
The physiological institute of the University Tübinge has succeeded in preventing vascular calcification in Klotho-deficient mice by inhibiting osteogenic signal transduction. The animals reach an almost normal life span despite increased 1.25 (OH) 2D3, Ca2 + and phosphate plasma concentrations. The male animals are again fertilized, but not the female animals. However, if the plasma concentrations of 1.25 (OH) 2D3 are normalized by administration of a vitamin-poor diet, the female animals are fertilized within two weeks. Further investigations revealed an inhibitory effect of 1.25 (OH) 2D3 on the implantation of the embryo. In the meantime the 1,25 (OH) 2D3-dependent signal transduction could be revealed, which prevents the implantation of the embryo. The vitamin D receptor and the elements of signal transduction are also expressed in the human endometrium. It is therefore possible that increased 1.25 (OH) 2D3 plasma concentrations also prevent embryo implantation in humans. ;
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