Vitamin-D dysregulation in early- and late-onset preeclampsia: A gestational-age matched study

Martin, Courtney; Oshiro, Bryan T.; Sands, LeeAnna D.; Kabir, Salma; Thorpe, Donna; Clark, Tatiana C.; Yao, Ruofan; Mata‐Greenwood, Eugenia

doi:10.1016/j.jsbmb.2020.105729

Cited by 8 publications

(13 citation statements)

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“…Longitudinal studies in BN rat pregnancies also showed mild-features of preeclampsia; we reported a rise in maternal blood pressure in day 14 of gestation with a 45 mm Hg increase by day 17, together with mild proteinuria [ 15 ]. An interesting feature of BN pregnancies is maternal 1,25-(OH) 2 -D deficiency [ 16 ] that has also been reported in preeclampsia [ 11 , 17 ]. Although it is thought that the cause of vitamin D deficiency is derived from a defective placenta, dysregulation of vitamin D metabolism has been observed at pre-pregnancy and postpartum stages in women that developed preeclampsia [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA was isolated from kidney sections with TRIzol reagent (Life Technologies) and subjected to reverse transcription using the Quantitect RT (Qiagen, Ca). The relative mRNA abundance of selected genes was determined by real time PCR using the QuantiTect SYBR green supermix (Qiagen, Ca) on the CFX Connect™ system (Bio-Rad) as previously described [ 17 ]. β-actin ( Actb ) was used an internal control; and negative controls (no template) were used in every run.…”

Section: Methodsmentioning

confidence: 99%

“…Maternal renal subcellular protein fractions for cytosol and nucleus were obtained using a subcellular protein fractionation kit for tissues (Pierce Thermo Fisher Scientific). Protein lysates were then analyzed by Western immune blotting, as previously described [ 17 ]. Briefly, the protein samples (50 μ g total extract, 30 μ g cytosolic extract or 15 μ g nuclear extract) were heat denatured in Laemmli buffer, separated on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and transferred to polyvinylidene fluoride membranes.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, other rat strains such as Sprague-Dawley and Lewis demonstrate a pregnancy-induced 2-fold increase of circulating 1,25-(OH) 2 -D and a 40% decrease in 25-OH-D levels with pregnancy [ 16 ]. This is of interest as preeclampsia that is associated with FGR shows a significant decrease in maternal plasma levels of 1,25-(OH) 2 -D with lesser decreases in 25-OH-D [ 13 , 17 ]. The kidney is a key organ in regulating the circulating levels of 1,25-(OH) 2 -D in all mammals [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Renal functional, transcriptome, and methylome adaptations in pregnant Sprague Dawley and Brown Norway rats

et al. 2022

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Pregnancy induces maternal renal adaptations that include increased glomerular filtration rate and renal blood flow which can be compromised in obstetrical complications such as preeclampsia. Brown Norway (BN) rat pregnancies are characterized by placental insufficiency, maternal hypertension, and proteinuria. We hypothesized that BN pregnancies would show renal functional, anatomical, or molecular features of preeclampsia. We used the Sprague-Dawley (CD) rat as a model of normal pregnancy. Pregnancy increased the glomerular filtration rate by 50% in CD rats and 12.2% in BN rats compared to non-pregnancy, and induced proteinuria only in BN rats. BN pregnancies showed a decrease in maternal plasma calcitriol levels, which correlated with renal downregulation of 1-alpha hydroxylase and upregulation of 24-hydroxylase. RNA sequencing revealed that pregnancy induced 297 differentially expressed genes (DEGs) in CD rats and 174 DEGs in BN rats, indicating a 70% increased response to pregnancy in CD compared to BN rats. Pregnancy induced activation of innate immune pathways such as ‘Role of Pattern Recognition Receptors’, and ‘Interferon signaling’ with interferon regulatory factor 7 as a common upregulated upstream factor in both rat strains. Comparison of rat strain transcriptomic profiles revealed 475 DEGs at non-pregnancy and 569 DEGs at pregnancy with 205 DEGs shared at non-pregnancy (36%), indicating that pregnancy interacted with rat strain in regulating 64% of the DEGs. Pathway analysis revealed that pregnancy induced a switch in renal transcriptomics in BN rats from ‘inhibition of renal damage’ to ‘acute phase reaction’, ‘recruitment of immune cells’ and ‘inhibition of 1,25-(OH)2-vitamin D synthesis’. Key upstream regulators included peroxisome-proliferator-activated receptor alpha (PPARA), platelet-derived growth factor B dimer (PDGF-BB), and NF-kB p65 (RELA). DNA methylome profiling by reduced representation bisulfite sequencing studies revealed that the DEGs did not correlate with changes in promoter methylation. In sum, BN rat kidneys respond to pregnancy-specific signals with an increase in pro-inflammatory gene networks and alteration of metabolic pathways including vitamin D deficiency in association with mild proteinuria and blunted GFR increase. However, the lack of glomerular endotheliosis and mild hypertension/proteinuria in pregnant BN rats limits the relevance of this rat strain for preeclampsia research.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Renal functional, transcriptome, and methylome adaptations in pregnant Sprague Dawley and Brown Norway rats

et al. 2022

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“…In addition, it cannot be excluded that the megalin-dependent uptake of the VDBP-25(OH)D complex into cells is limited to the proximal renal tubule. For example, a vitamin D-dependent expression megalin and cubilin has been found in several other epithelia including placenta, parathyroid glands, pneumocytes, and epididymal epithelial cells [93,[194][195][196].…”

Section: Role Of the Markermentioning

confidence: 99%

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance

et al. 2022

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Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC–MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC–MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.

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Vitamin D status and its association with parathyroid hormone in 23,134 outpatients

Chen

Chu

Doebis

et al. 2022

The Journal of Steroid Biochemistry and Molecular Biology

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Vitamin-D dysregulation in early- and late-onset preeclampsia: A gestational-age matched study

Cited by 8 publications

References 40 publications

Renal functional, transcriptome, and methylome adaptations in pregnant Sprague Dawley and Brown Norway rats

Renal functional, transcriptome, and methylome adaptations in pregnant Sprague Dawley and Brown Norway rats

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance

Vitamin D status and its association with parathyroid hormone in 23,134 outpatients

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