Endocrine-disrupting chemicals are natural and synthetic compounds found ubiquitously in the environment that interfere with the hormonal-immune axis, potentially impacting human health and reproduction. Exposure to endocrine-disrupting chemicals has been associated with numerous health risks, such as neurodevelopmental disorders, metabolic syndrome, thyroid dysfunction, infertility, and cancers. Nevertheless, the current approach to establishing causality between these substances and disease outcomes has limitations.
View Article and Find Full Text PDFHuman biomonitoring studies typically capture only a small and unknown fraction of the entire chemical universe. We combined chemical analysis with a high-throughput in vitro assay for neurotoxicity to capture complex mixtures of organic chemicals in blood. Plasma samples of 624 pregnant women from the German LiNA cohort were extracted with a nonselective extraction method for organic chemicals.
View Article and Find Full Text PDFHuman exposure to pesticides in the general population occurs mainly through food consumption. However, specific dietary habits or food products that contribute to pesticide exposure are often unknown. In this study, we propose a combined screening for polyphenols and pesticide residues by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to assess the diet and the associated pesticide exposure.
View Article and Find Full Text PDFPolybrominated diphenyl ethers (PBDEs), commonly used as synthetic flame retardants, are present in a variety of consumer products, including electronics, polyurethane foams, textiles, and building materials. Initial evidence from epidemiological and experimental studies suggests that maternal PBDE exposure may be associated with a higher BMI in children, with disturbance of energy metabolism and an increased risk of Type 2 diabetes. However, the causality between early exposure to real-life PBDE concentrations and increased weight as well as mechanisms underlying impaired metabolic pathways in the offspring remain elusive.
View Article and Find Full Text PDFIntroduction: More than 350,000 chemicals make up the chemical universe that surrounds us every day. The impact of this vast array of compounds on our health is still poorly understood. Manufacturers are required to carry out toxicological studies, for example on the reproductive or nervous systems, before putting a new substance on the market.
View Article and Find Full Text PDFAs a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties.
View Article and Find Full Text PDFImmune homeostasis is key to guarantee that the immune system can elicit effector functions against pathogens and at the same time raise tolerance towards other antigens. A disturbance of this delicate balance may underlie or at least trigger pathologies. Endocrine disrupting chemicals (EDCs) are increasingly recognized as risk factors for immune dysregulation.
View Article and Find Full Text PDFThe enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms.
View Article and Find Full Text PDFEndocrine disrupting chemicals (EDCs) possess the capability to interfere with the endocrine system by binding to hormone receptors, for example on immune cells. Specific effects have already been described for individual substances, but the impact of exposure to chemical mixtures during pregnancy on maternal immune regulation, placentation and fetal development is not known. In this study, we aimed to investigate the combined effects of two widespread EDCs, bisphenol A (BPA) and benzophenone-3 (BP-3), at allowed concentrations on crucial pregnancy processes such as implantation, placentation, uterine immune cell populations and fetal growth.
View Article and Find Full Text PDFPubertal mammary branching morphogenesis is a hormone-regulated process susceptible to exposure to chemicals with endocrine disruptive capacity, such as the UV-filter benzophenone-3 (BP3). Our aim was to assess whether intrauterine or in vitro exposure to BP3 modified the branching morphogenesis of the female mouse mammary gland. For this, pregnant mice were dermally exposed to BP3 (0.
View Article and Find Full Text PDFBackground: There is a growing need for immunological assays to test toxic and modulatory effects of chemicals. The assays should be easy to use, reproducible and superior to cell line-based assays. We have therefore developed a comprehensive portfolio of assays based on primary human blood cells that are suitable for testing chemical effects.
View Article and Find Full Text PDFHigher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium.
View Article and Find Full Text PDFThe prevalence of inflammatory bowel disease (IBD) is rising globally; however, its etiology is still not fully understood. Patient genetics, immune system, and intestinal microbiota are considered critical factors contributing to IBD. Preclinical animal models are crucial to better understand the importance of individual contributing factors.
View Article and Find Full Text PDFIn our experimental study we explored the impact of maternal reduced heme oxygenase-1 (HO-1) gene () expression on the fertilization (IVF) rate through the use of heterozygous Hmox1 knockout mice models (HET/Hmox1+/ -). Also, we hypothesized a beneficial role of gametes exposure during fertilization to carbon monoxide (CO), one of HO-1 by-products, that might be relevant for the improvement of IVF rates. IVF technique was performed by using oocytes obtained from wild-type (WT) or dams fertilized with WT, or mice-derived sperm.
View Article and Find Full Text PDFThe maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19, BMyD88 and µMT murine dams at gestational day 16 (gd 16).
View Article and Find Full Text PDFBackground: Humans are exposed to many different chemicals on a daily basis, mostly as chemical mixtures, usually from food, consumer products and the environment. Wastewater treatment plant effluent contains mixtures of chemicals that have been discarded or excreted by humans and not removed by water treatment. These effluents contribute directly to water pollution, they are used in agriculture and may affect human health.
View Article and Find Full Text PDFOvarian cancer has the highest mortality rate among female reproductive tract malignancies. A complex network, including the interaction between tumor and immune cells, regulates the tumor microenvironment, survival, and growth. The role of mast cells (MCs) in ovarian tumor pathophysiology is poorly understood.
View Article and Find Full Text PDFIn the last decades, per- and poly-fluoroalkyl substances (PFAS), widely used industrial chemicals, have been in the center of attention because of their omnipotent presence in water and soils worldwide. Although efforts have been made to substitute long-chain PFAS towards safer alternatives, their persistence in humans still leads to exposure to these compounds. PFAS immunotoxicity is poorly understood as no comprehensive analyses on certain immune cell subtypes exist.
View Article and Find Full Text PDFThis newly established 24-color (30-marker) panel focuses on the characterization of the main human immune cell subtypes and was optimized for the analysis of human whole blood using a full spectrum flow cytometer. The panel covers all main leukocyte populations: neutrophils, eosinophils and basophils, monocytes (with additional subsets), dendritic cells, innate lymphoid cells and lymphocytes. As for lymphocytes, this panel includes CD4+ T helper, Treg cells, and CD8+ cytotoxic T cells.
View Article and Find Full Text PDFBackground: To evaluate the benefits of SARS-CoV-2 vaccination in cancer patients it is relevant to understand the adaptive immune response elicited after vaccination. Patients affected by hematologic malignancies are frequently immune-compromised and show a decreased seroconversion rate compared to other cancer patients or controls. Therefore, vaccine-induced cellular immune responses in these patients might have an important protective role and need a detailed evaluation.
View Article and Find Full Text PDFVertical transmission of rubella virus (RuV) occurs at a high rate during the first trimester of pregnancy. The modes of vertical transmission including the response of trophoblasts to RuV are not well understood. Here, RuV-trophoblast interaction was studied in the BeWo trophoblast cell line.
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