Temporal expression of genes involved in folate metabolism and transport during placental development, preeclampsia and neural tube defects

Mohanraj, Palani Selvam; Rahat, Beenish; Mahajan, Aatish; Bagga, Rashmi; Kaur, Jyotdeep

doi:10.1007/s11033-019-04776-w

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…Interestingly, according to a study, women who smoke cigarettes throughout pregnancy are at a 33% reduced risk of developing this disorder (Bainbridge et al 2005 ). In addition, folate is an essential micronutrient during pregnancy, deficient folate status in association with alteration in expression of enzymes involved in folate metabolism might be associated with pregnancy complications such as pre-eclampsia and NTDs (Mohanraj et al 2019 ). We surmise that nicotine addiction and folate biosynthesis can also cause changes in gastrointestinal microbiome; the exact mechanisms through gastrointestinal microbiome that influence the risk of pre-eclampsia need to be studied ulteriorly.…”

Section: Discussionmentioning

confidence: 99%

The causal role of intestinal microbiome in development of pre-eclampsia

Xiong

Wang

Pei

et al. 2023

Funct Integr Genomics

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The correlation of pre-eclampsia (PE) and intestinal microbiome has been widely demonstrated in existing research, whereas their causal relationship has been rarely explored. The causal relationship between intestinal microbiome and PE risk was examined using large-scale genome-wide association studies (GWAS) summary statistics. To be specific, the causal microbial taxa for PE were identified using the two-sample Mendelian randomization (MR) method. The results were verified to be robust through comprehensive sensitive analyses, and the independence of causal relationship was ensured through novel multivariable MR analyses. The possibility of reverse relationships was ruled out through reverse-direction MR analyses. Lastly, the biofunction was explored through enrichment analysis, and a series of validations of PE results in a second GWAS were performed to confirm the results. After correction, four microbial taxa, including Streptococcus genus for PE (FDR q = 0.085), Olsenella genus for PE (FDR q = 0.085), Enterobacteriales order for PE (FDR q = 0.0134), and Akkermansia genus for PE (FDR q = 0.015), had a causal relationship to diverse joint PE (FDR q < 0.15). Moreover, when three different methods were employed on basis of the nominal significance (P < 0.05), five suggestive microbial taxa took on significance. The effect of heterogeneity and horizontal pleiotropy was excluded through sensitive analysis, and the possibility of horizontal pleiotropy of BMI was ruled out through multivariable MR analysis. The protective mechanism of the identified taxa against PE was illustrated through GO enrichment analysis and KEGG pathways. A number of microbial taxa had a causal relationship to PE. The result of this study provides more insights into intestinal microbiome in the pathology of PE.

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Section: Discussionmentioning

confidence: 99%

The causal role of intestinal microbiome in development of pre-eclampsia

Xiong

Wang

Pei

et al. 2023

Funct Integr Genomics

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“…Вместе с генами тромбофилии обычно исследуются гены фолатного цикла [10,18,19]. В этой системе мы не выявили никаких значимых различий между исследуемыми группами по частоте встречаемости полиморфных вариантов генов MTHFR, MTR, MTRR, CBS, несмотря на то, что в ряде научных публикаций продемонстрирова-ORIGINAL STUDY НАУЧНОЕ ИССЛЕДОВАНИЕ на связь данной генной сети с акушерской патологией [20][21][22]. Единственное статистически значимое различие среди генов фолатного цикла было получено по частоте встречаемости полиморфного гомозиготного генотипа СС гена SLC19A1 (rs1051266): в группе 1 данный вариант был выявлен у 21,9% (61/279) пациенток, а в группе 2у 11,6% (13/112) (χ 2 = 5,48; р = 0,019; ОШ = 2,13; 95%-й ДИ: 1,11-4,06).…”

Section: основные результаты исследованияunclassified

Predicting the Development of Great Obstetric Syndromes Based on Multilocus Genetic Analysis: Results of a Retrospective Comparative Cohort Study

et al. 2021

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Background. Great obstetric syndromes are pathological conditions, related to the level of maternal, perinatal and infant morbidity and mortality. There is a genetic component in the development of pregnancy complications, as evidenced by numerous clinical observations and research results. Purpose to study the frequency characteristics of the occurrence of polymorphic variants of various genes and their combinations in patients who underwent pregnancy complicated by great obstetric syndromes in comparison with women whose pregnancy proceeded without complications and successfully ended with the birth of a live full-term baby. Methods. A retrospective comparative cohort study was conducted. Molecular genetic research was carried out in 391 women: 279 women who underwent one of the verified clinical forms related to great obstetric syndromes (main group), 112 women were included in the control group. 37 polymorphisms in 33 genes were studied (FGB, F2, F5, F7, F13, GPIa, GPIIIa, GPVI, PROC, PAI1, PLAT, MTHFR, MTHFD, MTRR, MTR, SLC19A1, CBS, NOS3, END1, ACE, ADD1, AGT , CYP11B2, GSTM, GSTT, GSTP1, MnSOD, GPX1, IL1, TNF-a, ESR1, ESR2, PGR). Results. The most significant polymorphisms and their combinations were identified. In the main group, the following combinations were more common: ACE Alu I/D ID + AGT А704G GG, AGT А704G GG + MTRR A66G AG, F7 G10976A GG + AGT А704G GG, F7 G10976A GG + F13 G103A GG, F7 G10976A GG + GPIa С807T CC, F7 G10976A GG + MTHFR C677T CC, CYP11B2 G-344A GA + IL1 G+3953A GA, PAI1-657 5G/4G 5G4G + IL1 G+3953A AA, PAI1-657 5G/4G 4G4G + IL1 G+3953A AA, in control group AGT A704G AA + MTRR A66G AG, AGT A704G AG + MTRR A66G AG (the differences are statistically significant). To simplify the practical application of the analysis for genetic polymorphisms, a computer program named GOS RISK was created to assess the risk of pregnancy complications. The sensitivity and specificity were 70.8% and 78.8%, the efficiency of the method 74.8%. Conclusion. Analysis of individual polymorphic variants of genes indicates their role in the discussed pathology. Creation of computer programs based on multilocus genome analysis increases the predictive value of molecular genetic studies.

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“…19 Conversely, in fetuses with NTDs, an adaptive upregulation of placental FRα and RFC expression has been observed in response to low folate bioavailability. 20 However, it remains unclear if placental folate transport in fetuses with NTDs may be altered in regions with a low burden of folate deficiency, where maternal folate levels are likely adequate, and whether compromised placental folate transport may relate to the poor growth outcomes often experienced by these fetuses. [10][11][12] Here we aimed to better understand whether, and how, HBC phenotype and placental folate transport were altered in fetuses with isolated spina bifida (SB) compared to placentae from fetuses without congenital anomalies.…”

Section: Introductionmentioning

confidence: 99%

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

White,

Abdo,

Grynspan

et al. 2024

American J Rep Immunol

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ProblemFetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental‐mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate‐dependent placental macrophages.Method of studyFolate receptor‐α (FRα), proton coupled folate receptor (PCFT), and reduced folate carrier (RFC) protein localization and expression (immunohistochemistry) and HBC phenotypes (HBC abundance and folate receptor‐β [FRβ] expression; RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n = 12) and in term (n = 10) and gestational age (GA) – and maternal body mass index – matched (n = 12) controls without congenital anomalies.ResultsCases had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p = .0001) and higher average HBC FRβ expression (3.2 mRNA molecules per HBC vs. 2.3, p = .03) than GA‐matched controls. HBCs in cases were largely polarized to a regulatory phenotype (median 92.1% of HBCs). In sex‐stratified analyses, only male cases had higher HBC levels and HBC FRβ expression than GA‐matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabeling.ConclusionsHBC abundance and FRβ expression by HBCs are increased in placentae of fetuses with SB, suggesting immune‐mediated dysregulation in placental phenotype, and could contribute to SB‐associated comorbidities.

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Temporal expression of genes involved in folate metabolism and transport during placental development, preeclampsia and neural tube defects

Cited by 10 publications

References 37 publications

The causal role of intestinal microbiome in development of pre-eclampsia

The causal role of intestinal microbiome in development of pre-eclampsia

Predicting the Development of Great Obstetric Syndromes Based on Multilocus Genetic Analysis: Results of a Retrospective Comparative Cohort Study

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

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