Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

Dobierzewska, Aneta; Soman, Sony; Illanes, Sebastián E.; Morris, Andrew J.

doi:10.1371/journal.pone.0175118

Cited by 37 publications

(44 citation statements)

References 44 publications

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“…18 However, WTAP-independent methylation sites only exist at the 5′-UTR, and such methylations are reported to have a positive correlation with translation efficiency. 45,47 Especially in PE placentas, TGFβs are elevated. 46 In response to cellular stress, numerous additional domains show changes in m 6 A levels at the 5′-UTR, compared to those in the vicinity of the stop codon.…”

Section: Discussionmentioning

confidence: 99%

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

et al. 2019

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Intracellular mRNA levels are not always proportional to their respective protein levels, especially in the placenta. This discrepancy may be attributed to various factors including post-transcriptional regulation, such as mRNA methylation (N6methyladenosine: m 6 A). Here, we conducted a comprehensive m 6 A analysis of human placental tissue from neonates with various birth weights to clarify the involvement of m 6 A in placental biology. The augmented m 6 A levels at the 5′-untranslated region (UTR) in mRNAs of small-for-date placenta samples were dominant compared to reduction of m 6 A levels, whereas a decrease in m 6 A in the vicinity of stop codons was common in heavy-for-date placenta samples. Notably, most of these genes showed similar expression levels between the different birth weight categories. In particular, preeclampsia placenta samples showed consistently upregulated SMPD1 protein levels and increased m 6 A at 5′-UTR but did not show increased mRNA levels. Mutagenesis of adenosines at 5′-UTR of SMPD1 mRNAs actually decreased protein levels in luciferase assay. Collectively, our findings suggest that m 6 A both at the 5′-UTR and in the vicinity of stop codon in placental mRNA may play important roles in fetal growth and disease.

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Section: Discussionmentioning

confidence: 99%

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

et al. 2019

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“…The vaginal microenvironment also comprises both microbially and host‐produced metabolites that may influence clinical endpoints. Although the vaginal metabolome is largely influenced by resident microbiota, prior research has identified metabolites associated with important clinical conditions including BV, pre‐eclampsia, and preterm labour . More recently, Ilhan et al .…”

Section: Introductionmentioning

confidence: 99%

The vaginal metabolome and microbiota of cervical HPV‐positive and HPV‐negative women: a cross‐sectional analysis

Borgogna

Shardell

Santori

et al. 2019

BJOG

109

105

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Objective Characterise the vaginal metabolome of cervical HPVinfected and uninfected women.Design Cross-sectional.Sample Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV + ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV).Method Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. Main outcome measures Metabolite abundances.Results Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV + women had higher biogenic amine and phospholipid concentrations compared with HPVwomen after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV + and HPV À women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV + women than in HPVwomen. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV + participants than in HPVparticipants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). ConclusionsThe vaginal metabolome of HPV + women differed from HPV À women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. Keywords 16S rRNA gene amplicon sequencing, human papillomavirus, vaginal metabolome, vaginal microbiota. Tweetable abstract Metabolomics study: Vaginal microenvironment of HPV + women may be informative for nonsurgical interventions. Please cite this paper as: Borgogna JC, Shardell MD, Santori EK, Nelson TM, Rath JM, Glover ED, Ravel J, Gravitt PE, Yeoman CJ, Brotman RM. The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

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“…Other study demonstrated significant reduction of third trimester serum S1P levels in preeclampsia patients relative to controls (39). Cross-gestational sphingolipidomic analyses revealed significant reduction of dihydro-S1P levels, which are associated with endothelial barrier function, in second trimester plasma of preeclampsia patients, compared to their first trimester (40). These findings indicate that the impaired Sphk/S1P pathway may be involved in the pathogenesis of preeclampsia, particularly with respect to vascular defects.…”

Section: Discussionmentioning

confidence: 78%

Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase–deficient mice on 129Sv/C57BL/6 background

Mizugishi¹,

Yamashita²

2017

The FASEB Journal

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Exaggerated maternal immune responses must be strictly controlled to ensure a successful pregnancy. Neutrophil extracellular traps (NETs) have recently been implicated as a potential mechanism for promoting inflammation in pregnancy-related disorders. In this study, we demonstrated that NETs play a key role in the pathogenesis of sphingosine kinase (Sphk)-mediated pregnancy loss. Perturbing the sphingolipid pathway by disrupting genes during pregnancy led to excessive NET formation exclusively at the fetomaternal interface and early fetal death. Neutrophils that formed NETs were characterized by histone hypercitrullination and peptidylarginine deiminase 4 (PAD4) overexpression. In addition, thrombus formation was enhanced in the decidua, but not in the plasma, of-deficient mice. Blocking NET formation with a PAD4 inhibitor protected -deficient mice from pregnancy loss. The PAD4 inhibition significantly reduced the expression of hypercitrullinated histone in neutrophils and ameliorated vascular injury in the decidua of-deficient mice. Moreover, NET formation was induced in human neutrophils stimulated with Sphk-deficient human decidual cells. Together, these findings indicate that targeting NETs might be a novel therapeutic strategy to treat idiopathic pregnancy loss in humans.-Mizugishi, K., Yamashita, K. Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase-deficient mice on 129Sv/C57BL/6 background.

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Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia

Cited by 37 publications

References 44 publications

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

The vaginal metabolome and microbiota of cervical HPV‐positive and HPV‐negative women: a cross‐sectional analysis

Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase–deficient mice on 129Sv/C57BL/6 background

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