Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy

Sedlmeier, Eva-Maria; Brunner, Stefanie; Much, Daniela; Pagel, Philipp; Ulbrich, Susanne E.; Meyer, H. H. D.; Amann-Gassner, Ulrike; Hauner, Hans; Bader, B.

doi:10.1186/1471-2164-15-941

Cited by 58 publications

(66 citation statements)

References 82 publications

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“…It is plausible that the differential expression of placental genes by sex and diet accounts for the association. [40][41][42][43][44] Interestingly, the sex ratio of women with PAH versus non-PAH was equal in the study (data not shown). The exact mechanism through which fetal sex modifies dietary effects on PAH remains unclear.…”

Section: Discussionmentioning

confidence: 74%

Dietary patterns and the risk of pregnancy‐associated hypertension in the Danish National Birth Cohort: a prospective longitudinal study

Ikem

Halldorsson

Birgisdottir

et al. 2019

BJOG

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Objective To examine the association between midpregnancy dietary patterns and pregnancy-associated hypertension (PAH).Design A prospective longitudinal cohort study. Setting Denmark.Population About 55 139 Danish women with single enrolments and recorded food frequency questionnaire dates with complete information on dietary intake. Methods Women were eligible if they could speak Danish and were planning to carry to term. Diet was assessed using a validated semi-quantitative 360-item food frequency questionnaire and dietary patterns were derived using factor analysis.Main outcome measures Gestational hypertension (GH) and preeclampsia (PE).Results Disease prevalence was 14% for GH (5491/39 362); 2% for PE (1168/54 778), and 0.4% for severe PE (234/55 086). Seven dietary patterns were characterised in the population, of which two were associated with PAH. The Seafood diet characterised by high consumption of fish and vegetables was inversely associated with the odds of developing GH [odds ratio (OR) 0.86; 95% CI 0.77-0.95)] and PE (OR 0.79; 95% CI 0.65-0.97). The Western diet characterised by high consumption of potatoes (including French fries), mixed meat, margarine and white bread increased the odds of developing GH (OR 1.18; 95% CI 1.05-1.33) and PE (OR 1.40; 95% CI 1.11-1.76). No association was seen with severe PE. ConclusionsWe found protective associations of Seafood diet and harmful associations of Western diet with PAH. Dietary interventions encouraging the reduction of Western diet may contribute to a decrease of PAH.Tweetable abstract Western diet increases (Seafood diet decreases) the likelihood of developing pre-eclampsia among Danish pregnant women.

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Section: Discussionmentioning

confidence: 74%

Dietary patterns and the risk of pregnancy‐associated hypertension in the Danish National Birth Cohort: a prospective longitudinal study

Ikem

Halldorsson

Birgisdottir

et al. 2019

BJOG

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“…In murine models obesity alters placental morphology, cell proliferation and inflammation [44] and maternal diet alters placental gene expression [45] and epigenetic systems [46] in a sexually dimorphic manner. Maternal dietary n-3 polyunsaturated fatty acid administration gave sexually dimorphic changes in gene expression in placentas in mice [47] and in humans [41]. The underlying basis for these sexually dimorphic differences in gene expression in placenta remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphism in the effect of maternal obesity on antioxidant defense mechanisms in the human placenta

Evans

Myatt

2017

Placenta

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Introduction Maternal obesity creates an adverse intrauterine environment, negatively impacts placental respiration, is associated with a higher incidence of pregnancy complications and programs the offspring for disease in adult life in a sexually dimorphic manner. We defined the effect of maternal obesity and fetal sex on pro- and anti-oxidant status in placenta and placental mitochondria. Methods Placental villous tissue was collected at term via c-section prior to labor from four groups of patients based on fetal sex and prepregnancy/1st trimester body mass index: lean - BMI 22.1±0.3 (6 male, 6 female) and obese - BMI 36.3±0.4 (6 male, 6 female). Antioxidant enzyme activity, mitochondrial protein carbonyls, nitrotyrosine residues, total and nitrated superoxide dismutase (SOD) and nitric oxide synthesis were measured. Results Maternal obesity was associated with decreased SOD and catalase activity, and total antioxidant capacity (TAC), but increased oxidative (protein carbonyls) and nitrative (nitrotyrosine) stress in a sexually dimorphic manner. Placentas of lean women with a male fetus had higher SOD activity and TAC (p<0.05) than other groups whereas obese women with a male fetus had highest carbonyls and nitrotyrosine (p<0.05). Glutathione peroxidase and thioredoxin reductase activity increased with obesity, significantly with a male fetus, perhaps as a compensatory response. Conclusion Maternal obesity affects oxidative stress and antioxidant activity in the placenta in a sexually dimorphic manner. The male fetus of a lean women has the highest antioxidant activity, a protection which is lost with obesity perhaps contributing to the increased incidence of adverse outcomes with a male fetus.

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“…Higher miRNA expression would reduce expression of downstream target genes in placentas from folate‐deficient women; this was confirmed for ZEB2, MYC, and CDK6 at the mRNA level. Placental CDK6 expression positively correlates with birthweight , implying reduced expression under low folate conditions would negatively affect fetal growth. Reduced MYC and unaltered TP53 expression in placentas from women with low folate status contrast with FGR pregnancies, where both are elevated .…”

Section: Discussionmentioning

confidence: 99%

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

Baker

Mackie

Lean

et al. 2017

Molecular Nutrition Food Res

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ScopeLow maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression.Methods and resultsA prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy‐associated plasma protein A, progesterone, and human placental lactogen). miR‐222‐3p, miR‐141‐3p, and miR‐34b‐5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E‐box binding homeobox 2, v‐myc myelocytomatosis viral oncogene homolog (avian), and cyclin‐dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status.ConclusionThis study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate‐sensitive miRNAs and target genes as a mechanistic link.

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Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy

Cited by 58 publications

References 82 publications

Dietary patterns and the risk of pregnancy‐associated hypertension in the Danish National Birth Cohort: a prospective longitudinal study

Dietary patterns and the risk of pregnancy‐associated hypertension in the Danish National Birth Cohort: a prospective longitudinal study

Sexual dimorphism in the effect of maternal obesity on antioxidant defense mechanisms in the human placenta

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

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