Gestational diabetes mellitus modulates cholesterol homeostasis in human fetoplacental endothelium

Sun, Yidan; Kopp, Susanne; Strutz, Jasmin; Gali, Chaitanya Chakravarthi; Zandl-Lang, Martina; Fanaee-Danesh, Elham; Kirsch, Andrijana; Cvitic, Silvija; Frank, Saša; Saffery, Richard; Björkhem, Ingemar; Desoyé, Gernot; Wadsack, Christian; Panzenboeck, Ute

doi:10.1016/j.bbalip.2018.05.005

Cited by 32 publications

(39 citation statements)

References 64 publications

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“…This finding is consistent with other studies [16,43], which reported that LXR enhances maternal cholesterol delivery to the fetus. Thus, our data confirm the role of SR-B1 as an LXR-dependent mechanism controlling inward cholesterol uptake rates.…”

Section: Resultssupporting

confidence: 94%

“…The increase of ABCA1-mediated cholesterol efflux (~up to 2-fold) was less pronounced in comparison with the magnitude of ABCA1 mRNA upregulation (~up to 10-fold). A similar relationship between ABCA1 mRNA expression and apoA-1 dependent efflux was previously reported by others in trophoblasts [44] and in human fetoplacental endothelial cells [43]. …”

Section: Resultssupporting

confidence: 86%

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Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Kallol

Huang

Müller

et al. 2018

IJMS

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Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1) trophoblast monolayers grown on Transwell® system consisting of apical (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1-mediated cholesterol efflux operated almost exclusively at the apical-maternal side, where ABCA1 was also localized by immunofluorescence. We found greater cholesterol efflux capacity in STB, which was increased by liver-X-receptor agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother than in transfer to the fully developed fetus.

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Section: Resultssupporting

confidence: 94%

Section: Resultssupporting

confidence: 86%

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Kallol

Huang

Müller

et al. 2018

IJMS

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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%

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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“…In addition to the possible involvement of the nitric oxide signaling in this study, it would be interesting to evaluate the nitric oxide metabolites and the oxidative stress in these samples as well, since these pathways are affected in GDM and dyslipidemic pregnancies [54,[107][108][109]. However, what is happening with these parameters when they are present at the same time is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

et al. 2020

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Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

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Gestational diabetes mellitus modulates cholesterol homeostasis in human fetoplacental endothelium

Cited by 32 publications

References 64 publications

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

Novel Insights into Concepts and Directionality of Maternal–Fetal Cholesterol Transfer across the Human Placenta

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

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

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