Prepregnancy maternal diabetes combined with obesity impairs placental mitochondrial function involving Nrf2/ARE pathway and detrimentally alters metabolism of offspring

Yang, Dongzi; Sun, Fengze; Que, Shengshun; Li, Yueqin; Yang, Suyan; Liu, Geli

doi:10.1016/j.orcp.2017.01.002

Cited by 22 publications

(17 citation statements)

References 39 publications

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“…This process may be exacerbated by maternal diabetes mellitus, for the causal link between diabetic hyperglycemia and the production of reactive oxygen species (ROS) by mitochondria (31). Evidence has exhibited significant elevated formation of ROS and decreased superoxide dismutase (SOD) activities in placental tissues among pregnant women with pre-existing diabetes mellitus (32,33). Especially, in the Duan et al study (32), women with pregnancy complications (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence has exhibited significant elevated formation of ROS and decreased superoxide dismutase (SOD) activities in placental tissues among pregnant women with pre-existing diabetes mellitus (32,33). Especially, in the Duan et al study (32), women with pregnancy complications (e.g. pre-eclampsia) were excluded, and all placental tissues were obtained at the time of caesarean section in the absence of labour to minimize potential influence of vaginal delivery.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

Shu

Zhang

Cai

et al. 2020

Canadian Journal of Diabetes

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Key MessagesWe demonstrate the relationship between maternal diabetes and persistent pulmonary hypertension of newborns in a systematic review. The original studies were retrospective cohort or case-control studies, in which selection bias might exist. Variables (e.g. obesity, macrosomia, antidiabetic agents, antihypertensive agents, lifestyle changes) were often missing, which may influence outcomes.Keywords: diabetes mellitus persistent pulmonary hypertension of the newborn systematic review a b s t r a c t Objectives: Maternal diabetes mellitus (including pre-existing and gestational diabetes mellitus) is linked with adverse infant outcomes. However, the question of whether maternal diabetes increases the risk of persistent pulmonary hypertension of the newborn (PPHN) is unclear. Herein, we conducted a systematic review and meta-analysis to summarize clinical evidence to determine the association between maternal diabetes mellitus and PPHN. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, Cochrane Library, Web of Science and Google Scholar to identify relevant studies according to predefined criteria. Data from selected studies were extracted, and meta-analysis was performed using fixed effects modelling. Results: In all, we included 7 unique studies with aggregated data on 2 million individuals and >5,000 cases of PPHN. Maternal diabetes was significantly associated with a higher risk of PPHN (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.23 to 1.51). Both case-control and cohort studies exhibited that the presence of maternal diabetes increased the risk of PPHN (case-control: RR, 1.91; 95% CI, 1.02 to 2.79; cohort: RR, 1.36; 95% CI, 1.22 to 1.50). By omitting 1 study at a time, sensitivity analysis made sure that no individual study was entirely responsible for the combined results. Conclusions: Maternal diabetes was associated with increased risk of PPHN. For babies with refractory hypoxemia, with mothers with diabetes, PPHN should be taken into consideration in clinical practice. Ó 2019 The Author(s). Published on behalf of the Canadian Diabetes Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Mots clés: diabète sucré hypertension pulmonaire persistante du nouveau-né revue systématique r é s u m é Objectifs : Le diabète sucré maternel (notamment le diabète sucré préexistant et le diabète sucré gestationnel) est lié à des issues défavorables chez le nourrisson. Toutefois, on ignore si le diabète maternel

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

Shu

Zhang

Cai

et al. 2020

Canadian Journal of Diabetes

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“…As described in the BIntroduction^to this report, the heme oxygenase variant with most significant relevance to strategies for modulating the enzyme to prevent or treat disease, is HO-1, the inducible form which may function within cells (iHO-1), or extracellularly (eHO). Interestingly, iHO and eHO exhibit different-and in some cases, opposite modes of activity in T2DM pathogenesis, as revealed by a 2010 report which evaluated the role of plasma HO-1 concentrations as a modulator of oxidative stress in development of T2DM and comorbidities (Ban et al 2010)-and results of an investigation of obesity-related maternal diabetes-associated with mitochondrial impairment, reported in 2017, demonstrating that plasma eHO-1 was significantly decreased by T2DM in advance of pregnancy (Duan et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics

Mahmoud

Haines

Dashti

et al. 2018

Cell Stress and Chaperones

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Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

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“…A study revealed that cigarette smoke might inhibit the development of placenta via activation of ROS by inducing apoptosis and autophagy by affecting the expression of Keap1-Nrf2 expression [ 33 ]. In women with both type 2 diabetes mellitus and obesity, oxidative stress detrimentally alters placenta function and increase metabolic disturbance susceptibility in their offspring, in which the Nrf2/HO-1 pathway is involved [ 34 ]. Moreover, maternal fructose intake provoked an imbalanced redox status in placenta and a clear diminution of HO-1 expression, which could be responsible for the augmented oxidative stress found in their fetuses [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Damage and Nrf2 Translocation Induced by Toxicities of Deoxynivalenol on the Placental and Embryo on Gestation Day 12.5 d and 18.5 d

Wei

et al. 2018

Toxins

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Deoxynivalenol (DON) is a kind of natural pollutant belonging to the trichothecenes family. The aim of this study is to use diverse assays to evaluate oxidative damage as well as translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and to investigate their mechanisms in DON-induced toxicities on a placenta and embryo. Pregnant C57BL/6 mice were randomly assigned to three groups with different doses of DON: 0, 1.0, 2.5 mg/(kg·day). In gestation day (GD) 12.5 d and 18.5 d, DON induced an elevated resorption rate of the embryos as well as structural and functional damage of the placenta. In the placenta, altered levels of the antioxidant enzymes malondialdehyde, superoxide dismutase and glutathione indicated remarkable oxidative stress. Furthermore, an elevated level of heme oxygenase-1 (HO-1) and the translocation of Nrf2 from nucleus to cytoplasm indicated Nrf2/HO-1 pathway activation in DON-L group (1.0 mg/(kg·day)). It is noteworthy that the results in this experiment in GD 12.5 d were similar to those in GD 18.5 d. In conclusion, DON-induced placental oxidative damage and Nrf2 translocation were similar in GD 12.5 d and GD 18.5 d. Oxidative stress is one of the most important molecular mechanisms for embryotoxicity induced by DON, and Nrf2 translocation may play a substantial role against it.

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Prepregnancy maternal diabetes combined with obesity impairs placental mitochondrial function involving Nrf2/ARE pathway and detrimentally alters metabolism of offspring

Cited by 22 publications

References 39 publications

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics

Oxidative Damage and Nrf2 Translocation Induced by Toxicities of Deoxynivalenol on the Placental and Embryo on Gestation Day 12.5 d and 18.5 d

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