Miscarriages strongly associated with poor placental, decidua gene which locally activates Vitamin D

Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.

PLoS One. 2016 Dec 29; doi: 10.1371/journal.pone.0165589. eCollection 2016.

Wang LQ1,2, Yan XT1, Yan CF3, Zhang XW1,3, Hui LY4, Xue M5, Yu XW1.

1Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

2Nursing Department in Xi'an Medical College, Xi'an, China.

3Reproductive Center in Fourth Hospital of Xi'an, Xi'an, China.

4Laboratory Department in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

5Clinical Sciences Research Lab, Translational Medicine Section, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, University Hospital, Coventry, United Kingdom.

Facts about Vitamin D activation * Vitamin D must be activated before a majority of the benefits can be realized * Vitamin D can be activated by Liver & Kidney and put into the bloodstream * Vitamin D can also be activated locally by most tissues in the body * Local activation is not detected by Vitamin D tests * Vitamin D is activated by the fetus sometime during gestation Possibilities 1. Placenta itself needs activated vitamin D all during gestation 1. Fetus needs activated vitamin D before it’s liver and kidneys start functioning *     during the time in which miscarriages typically occur CYP27B1 RNA | | | | | | | --- | --- | --- | --- | --- | | Tissues | Control | Primary miscarriage, | Recurrent miscarriage | P | | Villous | 1.20 | 0.81 | 0.40 | 0.000 | | Decidual | 1.35 | 1.20 | 0.44 | 0.003 | Easy options to avoid miscarriages due to CYP27B1 restriction 1. Increase blood-levels of Vitamin D * e.g. Increase some/all of vitamin D supplements, sunshine, UV, Magnesium, Boron, Omega-3 1. Increase Vitamin D Receptor (which results in more Vitamin D getting into cells) * See VDR below in this window --- 1. 36+ VitaminDWiki pages have MISCARRIAGE in the title This list is automatically updated {LIST()} 1. Genetics category listing contains {include} 1. Vitamin D Receptor category contains {include}

Dec 2016 study

BACKGROUND:

Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM).

METHODS:

Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy.

RESULTS:

Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women.

CONCLUSIONS:

Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

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