The maternal body mass index and first-trimester placental (vascular) development.

Background: Maternal obesity is associated with maternal complications, including hypertensive disorders of pregnancy (HDP), and related fetal complications, such as fetal growth restriction. During pregnancy, the placenta is one of the key regulators of embryonic and fetal growth. Previous studies mainly investigated placental growth by measuring postpartum placental weight.

Diet-Induced Obesity in Mice Affects the Maternal Gut Microbiota and Immune Response in Mid-Pregnancy.

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)).

Differential effect of lead and cadmium on mitochondrial function and NLRP3 inflammasome activation in human trophoblast.

Heavy metals disrupt mitochondrial function and activate the NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the effect of lead (Pb)/cadmium (Cd) on mitochondrial function and NLRP3 inflammasome activation in human trophoblast under normoxic, hypoxic and pro-inflammatory conditions. JEG-3, BeWo and HTR-8/SVneo cells were exposed to Pb or Cd for 24 h in the absence or presence of hypoxia or pro-inflammatory lipopolysaccharide (LPS) or poly(I:C).

Decidual macrophages and Hofbauer cells in fetal growth restriction.

Placental macrophages, which include maternal decidual macrophages and fetal Hofbauer cells, display a high degree of phenotypical and functional plasticity. This provides these macrophages with a key role in immunologically driven events in pregnancy like host defense, establishing and maintaining maternal-fetal tolerance. Moreover, placental macrophages have an important role in placental development, including implantation of the conceptus and remodeling of the intrauterine vasculature.

Culturing Conditions Dictate the Composition and Pathways Enrichment of Human and Rat Perirenal Adipose-Derived Stromal Cells' Secretomes.

Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This study investigated changes in the secretome of perirenal ASC (prASC) under different conditions: normoxia, cytokine exposure, high glucose, hypoxia, and hypoxia with high glucose. Using mass spectrometry and enrichment clustering analysis, we found that normoxia enriched pathways related to extracellular matrix (ECM) organization, platelet degranulation, and insulin-like growth factor (IGF) transport and uptake.

The role of mesenchymal stem cells in early programming of adipose tissue in the offspring of women with obesity.

Maternal obesity is a well-known risk factor for developing premature obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes in the progeny. The development of white adipose tissue is a dynamic process that starts during prenatal life: fat depots laid down in utero are associated with the proportion of fat in children later on. How early this programming takes place is still unknown.

Cell type-dependent response to benzo(a)pyrene exposure of human placental cell lines under normoxic, hypoxic, and pro-inflammatory conditions.

Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various conditions. In this study, we aimed to investigate the effects of BaP on mitochondrial function, pyrin domain-containing protein 3 (NLRP3) inflammasome, and apoptosis in three human trophoblast cell lines under normoxia, hypoxia, and inflammatory conditions.

The intake of ultra-processed foods and homocysteine levels in women with(out) overweight and obesity: The Rotterdam Periconceptional Cohort.

Purpose: Today's diet consists of a substantial proportion of ultra-processed foods (UPF), especially in women with overweight and obesity in the reproductive period. High UPF intake results in an inadequate and unbalanced diet leading to derangements of several metabolic pathways detrimental to pregnancy and birth outcomes. Therefore, we aim to investigate whether UPF intake in the periconceptional period affects total homocysteine plasma levels (tHcy).

Exopolysaccharide β-(2,6)-levan-type fructans have a molecular-weight-dependent modulatory effect on Toll-like receptor signalling.

Scope: Fructans are a group of dietary fibers which are known to have many beneficial effects including immune-modulating effects. A family of fructans are β-(2,6)-linked levan-type fructans that are known to serve as exopolysaccharides in the cell wall of many species of bacteria including commensal bacteria and probiotics. It is still largely unknown whether and how they can serve as immunomodulating molecules.

Effects of polycyclic aromatic hydrocarbons (PAHs) on pregnancy, placenta, and placental trophoblasts.

Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants that are carcinogenic, mutagenic, endocrine-toxic, and immunotoxic. PAHs can be found in maternal and fetal blood and in the placenta during pregnancy. They may thus affect placental and fetal development.

The Effect of Antibiotics Treatment on the Maternal Immune Response and Gut Microbiome in Pregnant and Non-Pregnant Mice.

The gut microbiota are involved in adaptations of the maternal immune response to pregnancy. We therefore hypothesized that inducing gut dysbiosis during pregnancy alters the maternal immune response. Thus, pregnant mice received antibiotics from day 9 to day 16 to disturb the maternal gut microbiome.

Differences in Immune phenotype in decidual tissue from multigravid women compared to primigravid women.

Problem: Women with a previous uncomplicated pregnancy have lower risks of immune-associated pregnancy disorders in a subsequent pregnancy. This could indicate a different maternal immune response in multigravid women compared to primigravid women. In a previous study, we showed persistent higher memory T cell proportions with higher CD69 expression after uncomplicated pregnancies.

TLR2 and TLR4 activity in monocytes and macrophages after exposure to amoxicillin, ciprofloxacin, doxycycline and erythromycin.

Background: Antibiotics are used to treat bacterial infections but also impact immunity. This is usually attributed to antibiotic-induced dysbiosis of the microbiota, but antibiotics may have a direct effect on immune cells and immunity-associated receptors, such as Toll-like receptors (TLRs).

Objectives: To investigate whether antibiotics alter TLR2/1, TLR2/6 and TLR4 activity in immune cells.

Combining galacto-oligosaccharides and 2'-fucosyllactose alters their fermentation kinetics by infant fecal microbiota and influences AhR-receptor dependent cytokine responses in immature dendritic cells.

Galacto-oligosaccharides (GOS) and 2'-fucosyllactose (2'-FL) are non-digestible carbohydrates (NDCs) that are often added to infant formula to replace the functionalities of human milk oligosaccharides (HMOs). It is not known if combining GOS and 2'-FL will affect their fermentation kinetics and subsequent immune-modulatory effects such as AhR-receptor stimulation. Here, we used an set-up for the fermentation of 2'-FL and GOS, either individually or combined, by fecal microbiota of 8-week-old infants.

Maternal obesity during pregnancy leads to derangements in one-carbon metabolism and the gut microbiota: implications for fetal development and offspring wellbeing.

A healthy diet before and during pregnancy is beneficial in acquiring essential B vitamins involved in 1-carbon metabolism, and in maintaining a healthy gut microbiota. Each play important roles in fetal development, immune-system remodeling, and pregnancy-nutrient acquisition. Evidence shows that there is a reciprocal interaction between the one-carbon metabolism and the gut microbiota given that dietary intake of B vitamins has been shown to influence the composition of the gut microbiota, and certain gut bacteria also synthesize B vitamins.

Antidepressant use during pregnancy and development of preeclampsia: A focus on classes of action and specific transporters/receptors targeted by antidepressants.

Objective: The association between antidepressants and preeclampsia has been inconsistently reported. Given the compound-specific variable affinity for different transporters/receptors, their effect on preeclampsia risk could differ. Our study examined the risk of preeclampsia (and its subtypes) following exposure to different classes of antidepressants, also accounting for specific transporters/receptors targeted by antidepressants.

Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus.

A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth.

Chicory inulin enhances fermentation of 2'-fucosyllactose by infant fecal microbiota and differentially influences immature dendritic cell and T-cell cytokine responses under normal and Th2-polarizing conditions.

: Non-digestible carbohydrates (NDCs) such as native chicory inulin and 2'-fucosyllactose (2'-FL) are added to infant formula to mimic some of the human milk oligosaccharide (HMO) functions. It is unknown whether combining inulin and 2'-FL influences their fermentation kinetics and whether the immune-modulatory effects of these NDCs are different under normal and inflammatory-prone Th2-polarizing conditions. : We investigated the fermentation of 2'-FL and native chicory inulin, fermented individually and combined, using fecal inocula of 8-week-old infants.

Pectins that Structurally Differ in the Distribution of Methyl-Esters Attenuate Citrobacter rodentium-Induced Colitis.

Introduction: Pectins have anti-inflammatory properties on intestinal immunity through direct interactions on Toll-like receptors (TLRs) in the small intestine or via stimulating microbiota-dependent effects in the large intestine. Both the degree of methyl-esterification (DM) and the distribution of methyl-esters (degree of blockiness; DB) of pectins contribute to this influence on immunity, but whether and how the DB impacts immunity through microbiota-dependent effects in the large intestine is unknown. Therefore, this study tests pectins that structurally differ in DB in a mouse model with Citrobacter rodentium induced colitis and studies the impact on the intestinal microbiota composition and associated attenuation of inflammation.

Attenuation of Doxorubicin-Induced Small Intestinal Mucositis by Pectins is Dependent on Pectin's Methyl-Ester Number and Distribution.

Scope: Intestinal mucositis is a common side effect of the chemotherapeutic agent doxorubicin, which is characterized by severe Toll-like receptor (TLR) 2-mediated inflammation. The dietary fiber pectin is shown to prevent this intestinal inflammation through direct inhibition of TLR2 in a microbiota-independent manner. Recent in vitro studies show that inhibition of TLR2 is determined by the number and distribution of methyl-esters of pectins.

Structure-Specific Fermentation of Galacto-Oligosaccharides, Isomalto-Oligosaccharides and Isomalto/Malto-Polysaccharides by Infant Fecal Microbiota and Impact on Dendritic Cell Cytokine Responses.

Scope: Next to galacto-oligosaccharides (GOS), starch-derived isomalto-oligosaccharide preparation (IMO) and isomalto/malto-polysaccharides (IMMP) could potentially be used as prebiotics in infant formulas. However, it remains largely unknown how the specific molecular structures of these non-digestible carbohydrates (NDCs) impact fermentability and immune responses in infants.

Methods And Results: In vitro fermentation of GOS, IMO and IMMP using infant fecal inoculum of 2- and 8-week-old infants shows that only GOS and IMO are fermented by infant fecal microbiota.

Healthy and preeclamptic pregnancies show differences in Guanylate-Binding Protein-1 plasma levels.

The large interferon-inducible anti-angiogenic pro-inflammatory GTPase Guanylate Binding Protein-1 (GBP-1) is produced and secreted by activated endothelial cells and is highly induced by inflammatory cytokines and inhibited by angiogenic growth factors. During pregnancy a generalized mild inflammatory response is observed. During preeclampsia this generalized inflammatory response is even further activated and activation of the endothelium occurs.

Gestational diabesity and foetoplacental vascular dysfunction.

Gestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D-glucose and other nutrients, thereby negatively affecting the foetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre-pregnancy normal weight, viz.