Maternal Vitamin D Status in Preeclampsia: Seasonal Changes Are Not Influenced by Placental Gene Expression of Vitamin D Metabolizing Enzymes

Lechtermann, Carolin; Hauffa, Berthold P.; Herrmann, Ralf; Schündeln, Michael M.; Gellhaus, Alexandra; Grasemann, Corinna

doi:10.1371/journal.pone.0105558

Cited by 24 publications

(20 citation statements)

References 24 publications

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“…In contrast to previous reports describing decreased serum 25(OH)D3 in PET [13,14,31], vitamin D-deficiency was observed for most of the women in the current study, despite this being a predominantly white Caucasian cohort. This may be due to the smaller size and non-matched cohort used [14], or the fact that some studies quantified serum 25(OH)D3 using ELISA technology which cannot distinguish between 25(OH)D3 and 3- epi -25(OH)D3 and may therefore over-estimate serum vitamin D ‘status’ [13,31]. Nevertheless, the over-arching conclusion from data presented here is that simple measurement of serum 25(OH) D3 provides a very limited perspective of vitamin D in pregnancy.…”

Section: Discussioncontrasting

confidence: 99%

“…Previous studies have reported PET-associated declines in serum 1,25(OH) 2 D3 [31,32], similar to those reported in the current study. This may be due to decreased serum levels of insulin-like growth factor 1 [32], a stimulator of renal 1α-hydroxylase, or lower expression of 1α-hydroxylase in the placenta [33], but other PET studies have reported increased whole human placental tissue 1α-hydroxylase expression [34].…”

Section: Discussionsupporting

confidence: 90%

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Dysregulation of maternal and placental vitamin D metabolism in preeclampsia

et al. 2017

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Introduction Epidemiology has linked preeclampsia (PET) to decreased maternal serum 25-hydroxyvitamin D3 (25(OH)D3). However, alterations in systemic and placental/decidual transport and metabolism of 25(OH)D3 during pregnancy suggest that other forms of vitamin D may also contribute to the pathophysiology of PET. Methods In a cross sectional analysis of normal pregnant women at 1st (n = 25) and 3rd trimester (n = 21), pregnant women with PET (n = 22), and non-pregnant female controls (n = 20) vitamin D metabolites were quantified in paired maternal serum, placental, and decidual tissue. Results Serum 25(OH)D3 was not significantly different in sera across all four groups. In normal 3rd trimester pregnant women serum active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was significantly higher than non-pregnant, normal 1st trimester pregnant, and PET women. Conversely, PET sera showed highest levels of the catabolites 3-epi-25(OH)D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Serum albumin was significantly lower in normal 3rd trimester pregnant women and PET relative to normal 1st trimester pregnant women, but there was no change in free/bioavailable 25(OH)D3. In PET placental tissue, 25(OH)D3 and 3-epi-25(OH)D3 were lower than normal 3rd trimester tissue, whilst placental 24,25(OH)2D3 was highest in PET. Tissue 1,25(OH)2D3 was detectable in 1st trimester decidua, which also showed 10-fold higher 25(OH)D3 relative to paired placentae. 3-epi-25(OH)D3 and 24,25(OH)2D3 were not different for decidua and placenta. In normal 3rd trimester pregnant women, total, free and bioavailable maternal 25(OH)D3 correlated with placental 25(OH)D3, but this was not conserved for PET. Discussion These data indicate that PET is associated with decreased activation, increased catabolism, and impaired placental uptake of 25(OH)D3.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

Dysregulation of maternal and placental vitamin D metabolism in preeclampsia

et al. 2017

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“…The levels of 1,25-(OH)2D3 in the maternal and umbilical cord are lower in PE than Norm-Preg [57]. PE is more common in winter possibly due to low serum 25(OH)D3 and placental 1,25(OH) 2 D3 levels leading to impaired placentation [58] and up-regulation of TNF-α, IL-6 and IL-1β [59]. Vitamin D receptor null mice show increased plasma renin, plasma ngII, and HTN.…”

Section: Introductionmentioning

confidence: 99%

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Shah

Khalil

2015

Biochemical Pharmacology

153

124

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Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca2+, protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

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“…Большое количество генов регулируется с помощью кальцитриола [11,15]. VDR отвечают на воздействие кальцитриола увеличением генной экспрессии 25(OH)D -24-гидроксилазы (CYP24А1), чтобы метаболизировать 25(OH)D и 1,25(OH)2D в биологически инертные водорастворимые неактивные формы (в том числе кальцитроевую кислоту, она растворяется в воде и выводится из организма в составе желчи и мочи) [16][17][18]. Кальцитриол по механизму отрицательной обратной связи подавляет свой собственный синтез и стимулирует собственное разрушение за счет индукции почечного фермента 25-гидроксивитамин D-24-гидроксилазы (CYP24A1).…”

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The СYP24A gene expression the placental tissue during pregnancy

et al. 2016

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Aim. To study the nature of CYP24A1 gene expression in the placental tissue in women with different saturation of the body with vitamin D during normal pregnancy and preeclampsia.Materials and methods. Cohort retrospective and prospective study. There were examined 110 pregnant women in Saint Petersburg and Leningrad region, who took multivitamin complex containing 400 IU of vitamin D from 12 weeks of pregnancy. Time of inclusion is from September to June. All pregnant women were taken blood samples with the following determination of the level of 25-hydroxycalciferol, fragments of placental tissue with the following study of mRNA expression of CYP24A1 gene.Results. There were analyzed two groups of pregnant women. During the analysis of the saturation level of the body with vitamin D there were revealed the following things: the frequency of vitamin D deficiency in the main group was 69.6% in the group of comparison vitamin D deficiency was not found. The frequency of vitamin D insufficiency in the main group was 21.5% in the group of comparison – 18.5%. The frequency of the normal level of vitamin D in the main group was 8.9% in the group of comparison – 81.5%. Differences between the main group and the group of comparison are reliable (p < 0,0001). There revealed a statistically significant increase of the relative expression of mRNA of CYP24A1 gene in the placental tissue in women with preeclampsia (31,8 ± 20,6), in comparison with women with physiological pregnancy (11,2 ± 17,9) (p = 0.03)Conclusion. In women with preeclampsia low level of vitamin D in blood serum (less than 30 ng/ml) is 5 times more common, that is why insufficiency and deficiency of vitamin D in pregnant women can be attributed to risk factors for the development of preeclampsia. Expression of mRNA of CYP24A1 gene in placental tissue in patients with preeclampsia is three times higher in comparison with patients with a normal pregnancy. Thus, the increased expression of CYP24A1 gene in the placental tissue can be considered as one of the risk factors for the development of preeclampsia.

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Maternal Vitamin D Status in Preeclampsia: Seasonal Changes Are Not Influenced by Placental Gene Expression of Vitamin D Metabolizing Enzymes

Cited by 24 publications

References 24 publications

Dysregulation of maternal and placental vitamin D metabolism in preeclampsia

Dysregulation of maternal and placental vitamin D metabolism in preeclampsia

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

The СYP24A gene expression the placental tissue during pregnancy

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