Gene expression profiles in placenta and their association with anesthesia, delivery mode and maternal diabetes.

Introduction: Fetal development is dependent on placenta and affected by multiple factors including maternal diabetes. Here we aimed to identify maternal diabetes-associated changes in placentas and analyzed placental gene expression to understand its modulation by maternal diabetes and birth mode.

Methods: Placental RNAseq transcriptome analyses were performed on maternally-derived decidua and fetal-derived villous tissue from pregnancies of mothers with type 1 diabetes (n = 14), gestational diabetes (n = 6) and without diabetes (n = 14).

Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition.

Background: Previously, we revealed sexually dimorphic mRNA expression and responsiveness to maternal dietary supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in placentas from a defined INFAT study subpopulation. Here, we extended these analyses and explored the respective placental microRNA expression, putative microRNA-mRNA interactions, and downstream target processes as well as their associations with INFAT offspring body composition.

Results: We performed explorative placental microRNA profiling, predicted microRNA-mRNA interactions by bioinformatics, validated placental target microRNAs and their putative targets by RT-qPCR and western blotting, and measured amino acid levels in maternal and offspring cord blood plasma and placenta.

Maternal Type 1 Diabetes Reduces Autoantigen-Responsive CD4 T Cells in Offspring.

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process.

Allele-specific methylation of type 1 diabetes susceptibility genes.

The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype.

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies.

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age.

Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice.

Immune tolerance is executed partly by Foxp3(+)regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3(+)Treg-induction and prevention of islet autoimmunity in patients is still in its infancy.

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

Background: Previously we have examined the effect of maternal dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring fat mass. Considering the involvement of the placenta in fetal programming, we aimed to analyze the sex-specific gene expression in human term placenta and its response to the n-3 LCPUFA intervention, as well as their correlations to offspring adiposity.

Results: Placental gene expression was assessed in a control and n-3 LCPUFA intervention group by DNA microarrays, biological pathway analyses and RT-qPCR validation.

Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study.

Background: There is some evidence that the n-6/n-3 long-chain polyunsaturated fatty acids (LCPUFAs) ratio in early nutrition, and thus in breast milk, could influence infant body composition.

Methods: In an open-label randomized controlled trial (RCT), 208 healthy pregnant women were allocated to a dietary intervention (supplementation with 1,200 mg n-3 LCPUFAs per day and instructions to reduce arachidonic acid (AA) intake) from the 15th wk of gestation until 4 mo of lactation or to follow their habitual diet. Breast milk LCPUFAs at 6 wk and 4 mo postpartum were related to infant body composition assessed by skinfold thickness (SFT) measurements and ultrasonography during the first year of life.

Effect of reducing the n-6/n-3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition.

Objective: To investigate the effect of reducing the n-6/n-3 fatty acid ratio in maternal nutrition on the maternal and cord blood leptin axis and their association with infant body composition up to 2 years.

Design And Methods: 208 healthy pregnant women were randomized to either a dietary intervention to reduce the n-6/n-3 fatty acid ratio from 15th week of gestation until 4 months postpartum or a control group. Leptin, soluble leptin receptor and free leptin index were determined in maternal and cord plasma and related to infant body composition assessed by skinfold thicknesses up to 2 years.

Effect of reducing the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open-label randomized controlled trial.

Background: The composition of long-chain PUFAs (LCPUFAs) in the maternal diet may affect obesity risk in the mother's offspring.

Objective: We hypothesized that a reduction in the n-6 (omega-6):n-3 (omega-3) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life.

Design: In a randomized controlled trial, 208 healthy pregnant women were randomly assigned to an intervention (1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake) or a control diet from the 15th wk of pregnancy to 4 mo of lactation.

Functional characterization of promoter variants of the adiponectin gene complemented by epidemiological data.

Objective: Adiponectin (APM1, ACDC) is an adipocyte-derived protein with downregulated expression in obesity and insulin-resistant states. Several potentially regulatory single nucleotide polymorphisms (SNPs) within the APM1 gene promoter region have been associated with circulating adiponectin levels. None of them have been functionally characterized in adiponectin-expressing cells.

APOA5 variants and metabolic syndrome in Caucasians.

Apolipoprotein A5 (APOA5) gene variants were reported to be associated with two components of metabolic syndrome (MetS): higher TG levels and lower HDL levels. Moreover, a recent Japanese case-control study found variant -1131T>C associated with MetS itself. Thus, our study systematically analyzed the APOA5 gene for association with lipid parameters, any other features of MetS, including waist circumference, glucose-related parameters, blood pressure, uric acid, and MetS itself in Caucasians.

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg.

Objective: Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the development of several components of metabolic syndrome (MetS). The present study investigated the association of nine MCP-1 single nucleotide polymorphisms (SNPs) with MetS, type 2 diabetes mellitus and metabolic risk factors.

Subjects And Methods: The population-based study sample comprised 1630 subjects aged 55-74 years from KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4).