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Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level.

ABSTRACT: Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Increasing evidence shows that placentation defects may play important roles in GDM. However, our understanding of the human placenta remains limited. In this study, we generated a comprehensive transcriptomic profile of cellular signatures and transcriptomes in the human placenta in GDM using single-cell RNA sequencing (scRNA-seq), constructed a comprehensive cell atlas, and identified cell subtypes and subtype-specific marker genes. In addition, we investigated the placental cellular function and intercellular interactions in GDM. These findings help to elucidate the molecular mechanisms of GDM, and may facilitate the development of new approaches to GDM treatment and prevention.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8139321 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level.

Yang Yuqi Y Guo Fang F Peng Yue Y Chen Rong R Zhou Wenbo W Wang Huihui H OuYang Jun J Yu Bin B Xu Zhengfeng Z

Frontiers in endocrinology 20210507

Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Increasing evidence shows that placentation defects may play important roles in GDM. However, our understanding of the human placenta remains limited. In this study, we generated a comprehensive transcriptomic profile of cellular signatures and transcriptomes in the human placenta in GDM using single-cell RNA sequencing (scRNA-seq), constructed a comprehensive cell atlas, and identified cell s ...[more]

PMID: 34025588

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Project description:BackgroundThe micronutrient iodine is essential for a healthy intrauterine environment and is required for optimal fetal growth and neurodevelopment. Evidence linking urinary iodine concentrations, which mainly reflects short-term iodine intake, to gestational diabetes mellitus (GDM) is inconclusive. Although the placental concentrations would better reflect the long-term gestational iodine status, no studies to date have investigated the association between the placental iodine load and the risk at GDM. Moreover, evidence is lacking whether placental iodine could play a role in biomarkers of insulin resistance and β-cell activity.MethodsWe assessed the incidence of GDM between weeks 24 and 28 of gestation for 471 mother-neonate pairs from the ENVIRONAGE birth cohort. In placentas, we determined the iodine concentrations. In maternal and cord blood, we measured the insulin concentrations, the Homeostasis Model Assessment (HOMA) for insulin resistance (IR) index, and β-cell activity. Logistic regression was used to estimate the odds ratios (OR) of GDM, and the population attributable factor (PAF) was calculated. Generalized linear models estimated the changes in insulin, HOMA-IR, and β-cell activity for a 5 μg/kg increase in placental iodine.ResultsHigher placental iodine concentrations decreased the risk at GDM (OR = 0.82; 95%CI 0.72 to 0.93; p = 0.003). According to the PAF, 54.2% (95%CI 11.4 to 82.3%; p = 0.0006) of the GDM cases could be prevented if the mothers of the lowest tertile of placental iodine would have placental iodine levels as those belonging to the highest tertile. In cord blood, the plasma insulin concentration was inversely associated with the placental iodine load (β = - 4.8%; 95%CI - 8.9 to - 0.6%; p = 0.026).ConclusionsHigher concentrations of placental iodine are linked with a lower incidence of GDM. Moreover, a lower placental iodine load is associated with an altered plasma insulin concentration, HOMA-IR index, and β-cell activity. These findings postulate that a mild-to-moderate iodine deficiency could be linked with subclinical and early-onset alterations in the normal insulin homeostasis in healthy pregnant women. Nevertheless, the functional link between gestational iodine status and GDM warrants further research.

Dataset Information

Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level.

Publications

Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level.

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