Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status

Baker, Barbara S.; Mackie, Fiona L.; Lean, Samantha C.; Greenwood, Susan; Heazell, Alexander; Forbes, Karen; Jones, Rebecca L.

doi:10.1002/mnfr.201600646

Cited by 29 publications

(23 citation statements)

References 52 publications

(72 reference statements)

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“…Examination of differentially expressed exosomal miRNA in PTB samples provided more distinct clusters than for normal birth. A summary of functional roles already reported for many of the miRNAs identified in exosomes from PTB suggests that miRNAs are functionally linked to cell cycle regulation (let-7a-2-5p) (38, 39), MAPK kinase kinases and inhibition of cell growth (miR-520a-3p) (40), cellular transitions and inflammation (miR-520a-3p and miR-483-3p) (41, 42), placental oxidative stress response and impairment of mitochondrial function (miR-130b-3p and miR-4433b-3p) (43, 44), macrophage programming contributing to inflammatory and oxidative stress damages (miR-142-5p) (45), preeclampsia (miR-342-3p) (46, 47), as well as placental dysfunction and impaired fetal growth due to folate deficiency (miR-222-3p) (48).…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

et al. 2018

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Despite decades of research in the field of human reproduction, the mechanisms responsible for human parturition still remain elusive. The objective of this study was to describe the changes in the exosomal miRNA concentrations circulating in the maternal plasma between mothers delivering term and preterm neonates, across gestation using a longitudinal study design. This descriptive study identifies the miRNA content in exosomes present in maternal plasma of term and preterm birth (PTB) (n = 20 and n = 10 per each gestational period, respectively) across gestation ( i.e. , first, second, and third trimesters and at the time of delivery). Changes in exosomal miRNA signature in maternal plasma during term and preterm gestation were determined using the NextSeq 500 high-output 75 cycles sequencing platform. A total of 167 and 153 miRNAs were found to significantly change ( P < 0.05) as a function of the gestational age across term and PTB pregnancies, respectively. Interestingly, a comparison analysis between the exosomal miRNA profile between term and PTB reveals a total of 173 miRNAs that significantly change ( P < 0.05) across gestation. Specific trends of changes ( i.e. , increase, decrease, and both) as a function of the gestational age were also identified. The bioinformatics analyses establish that the differences in the miRNA profile are targeting signaling pathways associated with TGF- β signaling, p53, and glucocorticoid receptor signaling, respectively. These data suggest that the miRNA content of circulating exosomes in maternal blood might represent a biomolecular “fingerprint” of the progression of pregnancy.

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Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

et al. 2018

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“…Our hypothesis is that folate deficiency leads to PTB [27] and SGA [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], but further studies are necessary to better investigate the potential protective role of adequate folate intake and/or folic acid supplementation. To fill this gap, the primary aim of the current study was to describe the prevalence of dietary folate intake and its determinants among pregnant women from Catania (Italy).…”

Section: Introductionmentioning

confidence: 99%

Dietary Folate Intake and Folic Acid Supplements among Pregnant Women from Southern Italy: Evidence from the “Mamma & Bambino” Cohort

Barchitta

Maugeri

Lio

et al. 2020

IJERPH

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Folate requirement among women who plan to become pregnant should be raised to 600 μg/day during the periconceptional period. To meet this need, several countries began to promote the use of folic acid supplements before and during pregnancy. Here, we investigated prevalence and determinants of dietary folate intake and folic acid supplement use among 397 pregnant women (aged 15–50 years old, median = 37 years old). We also investigated their effects on neonatal outcomes in a subgroup of women who completed pregnancy. For doing that, we used data from the “Mamma & Bambino” project, an ongoing mother-child cohort settled in Catania (Italy). Inadequate folate intake was evaluated using a Food Frequency Questionnaire and defined as an intake < 600 μg/day. Women were also classified as non-users (i.e., women who did not use folic acid supplements), insufficient users (i.e., women who did not take folic acid supplements as recommended), and recommended users of folic acid supplements. Neonatal outcomes of interest were preterm birth (PTB) and small for gestational age (SGA). Nearly 65% of women (n = 257) reported inadequate folate intake, while 74.8% and 22.4% were respectively classified as insufficient or recommended users of supplements. We demonstrated higher odds of inadequate folate intake among smoking women (OR = 1.457; 95%CI = 1.046–2.030; p = 0.026), those who followed dietary restrictions (OR = 2.180; 95%CI = 1.085–4.378; p = 0.029), and those with low adherence to the Mediterranean Diet (OR = 3.194; 95%CI = 1.958–5.210; p < 0.001). In a subsample of 282 women who completed pregnancy, we also noted a higher percentage of SGA among those with inadequate folate intake (p < 0.001). Among 257 women with inadequate folate intake, those with low educational level were more likely to not take folic acid supplements than their more educated counterpart (OR = 5.574; 95%CI = 1.487–21.435; p = 0.012). In a subsample of 184 women with inadequate folate intake and complete pregnancy, we observed a higher proportion of SGA newborns among women who did not take supplement before pregnancy and those who did not take at all (p = 0.009). We also noted that the proportion of PTB was higher among non-users and insufficient users of folic acid supplements, but difference was not statistically significant. Our study underlined the need for improving the adherence of pregnant women with recommendations for dietary folate intake and supplement use. Although we proposed a protective effect of folic acid supplement use on risk of SGA, further research is encouraged to corroborate our findings and to investigate other factors involved.

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“…Tang et al found miR-141 up-regulated in fetal growth restriction (FGR) by down-regulating its target genes [27]. Baker et al reported low maternal folate status is associated with higher incidence of small for gestation age (SGA) infants, with elevated level of miR-141-3p in placental tissues [28]. Interestingly, they also found that trophoblast proliferation was increased in low maternal folate status, to some extend that is consistent with our results i.e.…”

Section: Discussionmentioning

confidence: 99%

Elevated microRNA-141-3p in placenta of non-diabetic macrosomia regulate trophoblast proliferation

et al. 2018

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BackgroundSeveral studies have reported microRNAs (miRNAs) could regulate the placental development, though the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear.MethodsTo identify the aberrantly expressed key miRNAs in placenta of NDFMS, we employed a strategy consisting of initial screening with miRNA microarray and further validation with quantitative RT-PCR assay (qRT-PCR). In vitro cellular model and a mouse pregnancy model were used to delineate the functional effects of key miRNA on proliferation, invasion, and migration.FindingsmiR-141-3p was identified as the key miRNA with expression level significantly higher in placentas of NDFMS compared with those from normal controls. Overexpressed miR-141-3p in HTR-8/SVneo cells contributed to increased cell proliferation, invasion, and migration. miR-141-3p inhibition in HTR-8/SVneo cells resulted in decreased cell proliferation and invasion. Significantly increased infant birth weight was observed in late pregnancy of C57BL/6J mice treated with miR-141-3p agomir. However, no significant difference was found in early pregnancy of C57BL/6J mice treated with miR-141-3p agomir.InterpretationmiR-141-3p could stimulate placental cell proliferation to participate in the occurrence and development of NDFMS.

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Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status

Cited by 29 publications

References 52 publications

Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

Dietary Folate Intake and Folic Acid Supplements among Pregnant Women from Southern Italy: Evidence from the “Mamma & Bambino” Cohort

Elevated microRNA-141-3p in placenta of non-diabetic macrosomia regulate trophoblast proliferation

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