Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial-Mesenchymal Transition Process.

We aimed to explore the relationship of adipose tissue concentrations of some persistent organic pollutants (POPs) with the risk of endometriosis and the endometriotic tissue expression profile of genes related to the endometriosis-related epithelial-mesenchymal transition (EMT) process. This case-control study enrolled 109 women (34 cases and 75 controls) between January 2018 and March 2020. Adipose tissue samples and endometriotic tissues were intraoperatively collected to determine concentrations of nine POPs and the gene expression profiles of 36 EMT-related genes, respectively.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

Background: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated.

Objective: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies.

Methods: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry.

Expression Profiles of Genes Related to Development and Progression of Endometriosis and Their Association with Paraben and Benzophenone Exposure.

Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs).

Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies.

Background: Perfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited.

Aim: To investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents.

PFAS association with kisspeptin and sex hormones in teenagers of the HBM4EU aligned studies.

Exposure to Perfluoroalkyl acids (PFAS) can impair human reproductive function, e.g., by delaying or advancing puberty, although their mechanisms of action are not fully understood.

Xeno-estrogenic activity of real-life mixtures of perfluoroalkylated substances in human placenta homogenates.

Humans are simultaneously exposed to complex chemical mixtures, and its combined effect can affect human health. As part of the HBM4EU project, the actual mixture of perfluoroalkylated substances (PFAS) in 25 human placenta samples was extracted by chromatographic methods and assessed for xeno-estrogenic activity using two in-vitro bioassays: the estrogen receptor transactivity and the E-Screen assay. Most of the PFAS extracts displayed xeno-estrogenic activity, in one or both assays.

Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males.

Background: Perfluoroalkyl substances (PFAS) are found in a wide range of consumer products. Exposure to PFAS in children and adolescents may be associated with alterations in thyroid hormones, which have critical roles in brain function.

Objective: This study investigated the association between plasma concentrations of PFAS and serum levels of total triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) in adolescent males.

Exposure to non-persistent pesticides and sexual maturation of Spanish adolescent males.

Background: Several non-persistent pesticides are endocrine disrupting chemicals and may impact on sexual maturation.

Objective: To examine the association between urinary biomarkers of non-persistent pesticides and sexual maturation in adolescent males in the Environment and Childhood (INMA) Project.

Methods: The metabolites of several pesticides were measured in spot urine samples collected from 201 boys aged 14-17 years, including: 3,5,6-trichloro-2-pyridinol (TCPy), metabolite of chlorpyrifos; 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), metabolite of diazinon; malathion diacid (MDA), metabolite of malathion; diethyl thiophosphate (DETP) and diethyl dithiophosphate, non-specific metabolites of organophosphates; 3-phenoxybenzoic acid (3-PBA) and dimethyl cyclopropane carboxylic acid, metabolites of pyrethroids; 1-naphthol (1-NPL), metabolite of carbaryl; and ethylene thiourea (ETU), metabolite of dithiocarbamate fungicides.

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge.

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies.

Development and validation of brain-derived neurotrophic factor measurement in human urine samples as a non-invasive effect biomarker.

Background: Brain-derived neurotrophic factor (BDNF), a neurotrophic growth factor mainly expressed in the brain, has been proposed as a potential effect biomarker; that is, as a measurable biomarker whose values could be associated with several diseases, including neurological impairments. The European Human Biomonitoring Initiative (HBM4EU) has also recognized effect biomarkers as a useful tool for establishing link between exposure to environmental pollutants and human health. Despite the well-establish protocol for measuring serum BDNF, there is a need to validate its assessment in urine, a non-invasive sample that can be easily repeated over time.

Kisspeptin as potential biomarker of environmental chemical mixture effect on reproductive hormone profile: A pilot study in adolescent males.

Background: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental chemicals adversely affect the human reproductive system.

Objective: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent males.

Methods: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals (arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6-methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fungicides (ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15-17 years from the INMA-Granada cohort.

Concentrations and predictors of aluminum, antimony, and lithium in breast milk: A repeated-measures study of donors.

Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015-2018) and analyzed for Al, Sb, and Li concentrations.

Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort.

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010-2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS).

The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace.

The human connection: First evidence of microplastics in remote high mountain lakes of Sierra Nevada, Spain.

Microplastics have become one of the most serious global threats to animal and human health. While their presence has been documented in all Earth water ecosystems, including remote mountain lakes, the observation that the abundance of microplastics is largely different across nearby lakes has rarely been examined. As part of a citizen science initiative, this study analyzed for the first time the abundance of microplastics in the surface of 35 glacial lakes of Sierra Nevada National Park in Southern Spain with the objective of determining the local factors that control their abundance.

The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells.

Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM-10 µM).

Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach.

Background: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures.

Objectives: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents.

Concentrations and determinants of lead, mercury, cadmium, and arsenic in pooled donor breast milk in Spain.

Aim: To measure concentrations of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in longitudinally collected donor breast milk samples and to determine associated factors.

Methods: Pb, Hg, Cd, and As concentrations were measured in 242 pooled breast milk samples from 83 donors to a Human Milk Bank in Spain, in 2015-2018, determining their association with the donors' sociodemographic profile, dietary and lifestyle habits, and post-partum time, among other factors, and with the nutritional characteristics of samples. Mixed-effect linear regression was used to identify predictors of Hg and As concentrations in breast milk and mixed-effect logistic regression to identify predictors of the presence of Pb and Cd.

BDNF as a potential mediator between childhood BPA exposure and behavioral function in adolescent boys from the INMA-Granada cohort.

Background: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF).

Objective: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain).

Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study.

Background: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: We designed a case-cohort study within the EPIC-Spain cohort.

Concentrations of perfluoroalkyl substances in donor breast milk in Southern Spain and their potential determinants.

Background: Breast milk is considered to offer the best nutrition to infants; however, it may be a source of exposure to environmental chemicals such as perfluoroalkyl compounds (PFAS) for breastfeeding infants. PFAS are a complex group of synthetic chemicals whose high stability has led to their ubiquitous contamination of the environment.

Objective: To assess the concentrations and profiles of PFAS in breast milk from donors to a human milk bank and explore factors potentially related to this exposure.

Bisphenol F and bisphenol S promote lipid accumulation and adipogenesis in human adipose-derived stem cells.

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as substitutes for bisphenol A (BPA), an endocrine disrupting chemical (EDC) with obesogenic activity. We investigated the in vitro effects of BPS and BPF on the adipogenesis of human adipose-derived stem cells (hASCs) exposed to different doses (0.01, 0.

Urinary metabolites of non-persistent pesticides and serum hormones in Spanish adolescent males.

Objective: To assess the relationship of urinary concentrations of ethylenethiourea (ETU), the main degradation product of ethylene bis-dithiocarbamate fungicides, 3-phenoxybenzoic acid (3-PBA), a common metabolite of many pyrethroids, and 1-naphthol (1N), a metabolite of the carbamate insecticide carbaryl, with hormone concentrations in adolescent males; and to examine interactions between pesticide metabolites and polymorphisms in xenobiotic metabolizing enzymes, including CYP2C19 and CYP2D6, in relation to hormone concentrations.

Methods: A cross-sectional study was conducted in 134 males from the Spanish Environment and Childhood (INMA)-Granada cohort. Urine and serum samples were collected from participants during the same clinical visit at the age of 15-17 years.