Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes

Martino, Jole; Sebért, Sylvain; Segura, María Teresa; García-Valdés, Luz; Florido, J.; Padilla, M. C.; Marcos, Ascensión; Rueda, Ricardo; McArdle, Harry J; Budge, Helen; Symonds, Michael; Campoy, Cristina

doi:10.1210/jc.2015-2590

Cited by 105 publications

(94 citation statements)

References 81 publications

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“…Our finding of reduced AMPK in placental tissue of GDM offspring extends and supports the work of Martino et al [47] who reported reduced AMPK (PRKAA1) mRNA in placentae of gestational diabetic pregnancies. Muralimanoharan et al [48] reported a reduction in phosphorylated AMPK in placentae of women with GDM, but no change in total AMPK protein.…”

Section: Discussionsupporting

confidence: 92%

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

et al. 2016

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We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452-5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase α1 (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease.

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Section: Discussionsupporting

confidence: 92%

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

et al. 2016

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“…It is consistent with previous reports where the TBARS levels were similar between the GDM and NPW placentas [19], and protein carbonyl formation was lower in the placentas of overweight patients compared to lean individuals [20], and more importantly, catalase and glutathione reductase (GSR) mRNA expression was higher in women with GDM compared with NPW [7]. Moreover, the TBARS and SOD concentrations were similar between the placentas from GDM and NPW [21].…”

Section: Discussionsupporting

confidence: 91%

“…Moreover, increased nitration levels of MAPK and consequently reduced catalytic activity [23], suggesting a reduction of both the GLUT4 protein expression and mitochondrial biogenesis. Others found reduced gene expression for AMPK and mTOR in GDM placentas, but these authors did not determine protein expression [19]. Therefore, in the present study mitochondria content was indirectly determined by measuring the COX4 expression and ATPase activity.…”

Section: Discussionmentioning

confidence: 82%

Mitochondrial content, oxidative, and nitrosative stress in human full-term placentas with gestational diabetes mellitus

Ramı́rez-Emiliano

Fajardo-Araujo

Zúñiga-Trujillo

et al. 2017

Reprod Biol Endocrinol

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BackgroundThe purpose of this study was to determine the mitochondrial content, and the oxidative and nitrosative stress of the placenta in women with gestational diabetes mellitus (GDM).MethodsFull-term placentas from GDM and healthy pregnancies were collected following informed consent. The lipid peroxidation (TBARS) and oxidized protein (carbonyls) levels were determined by spectrophotometry, and 3-nitrotyrosine (3-NT), subunit IV of cytochrome oxidase (COX4), adenosine 5′-monophosphate (AMP)–activated protein kinase (AMPK) and actin were determined by western blot, whereas ATPase activity was performed by determining the adenosine triphosphate (ATP) consumption using a High-performance liquid chromatography (HPLC) system.ResultsTBARS and carbonyls levels were lower in the placentas of women with GDM compared with the normal placentas (p < 0.001 and p < 0.05, respectively). Also, 3-NT/actin and AMPK/actin ratios were higher in GDM placentas than in the normal placentas (p = 0.03 and p = 0.012, respectively). Whereas COX4/actin ratio and ATPase activity were similar between GDM placentas and those controls.ConclusionsThese data suggest that placentas with GDM are more protected against oxidative damage, but are more susceptible to nitrosative damage as compared to normal placentas. Moreover, the increased expression levels of AMPK in GDM placentas suggest that AMPK might have a role in maintaining the mitochondrial biogenesis at normal levels.Trial registration HGRL28072011. Registered 28 July 2011.

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“…Thus, it is unclear if there is truly an unexpected normalization in neonates of obese class I compared to overweight mothers. One mechanism to explain this finding would be the concept of protective adaptation 19 which is overwhelmed in extreme obesity. We also evaluated the possibility of clinical sequelae affecting our results.…”

Section: Discussionmentioning

confidence: 99%

“…18 Given the morbidities associated with excessive maternal weight and our understanding of the relationship between adiposity and inflammation, it has been postulated that maternal obesity causes increased intrauterine inflammation in both fetal and placental circuits. 19-21 However, there are limited data available on the effect of maternal obesity on neonatal inflammatory markers and immunoglobulin (Ig) levels such that specific aspects of this pathophysiology remain uncertain. 10, 20-24 …”

Section: Introductionmentioning

confidence: 99%

Impact of parental obesity on neonatal markers of inflammation and immune response

et al. 2016

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Background/Objectives Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates. Subjects/Methods In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of 5 pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences (β) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared to normal weight. Results Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight, and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI≥35) were associated with increased neonatal inflammation scores (β=0.12, 95% CI: 0.02, 0.21; p=0.02, and β=0.13, CI: −0.002, 0.26; p=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels (β=0.11, CI: 0.04, 0.17; p=0.001 and β=0.12, CI: 0.05, 0.19); p<0.001, respectively). Paternal groups of overweight, obese class I and obese class II/III had decreased neonatal IgM levels (β=−0.08, CI: −0.13,-0.03, p=0.001; β=−0.07, CI: −0.13, −0.01, p=0.029 and β=−0.11, CI:−0.19,-0.04, p=0.003, respectively). Conclusions Excessive maternal weight was generally associated with increased inflammation and IgM supporting previous observations of maternal obesity and immune dysregulation in offspring. The role of paternal obesity requires further study.

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Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes

Cited by 105 publications

References 81 publications

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

Mitochondrial content, oxidative, and nitrosative stress in human full-term placentas with gestational diabetes mellitus

Impact of parental obesity on neonatal markers of inflammation and immune response

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