Endocrine disruptors: Challenges and future directions in epidemiologic research.
Ho V,Pelland-St-Pierre L,Gravel S,Bouchard M F,Verner M-A,Labrèche F
Environmental research
Public concern about the impact of endocrine disrupting chemicals (EDCs) on both humans and the environment is growing steadily. Epidemiologic research provides key information towards our understanding of the relationship between environmental exposures like EDCs and human health outcomes. Intended for researchers in disciplines complementary to epidemiology, this paper highlights the importance and challenges of epidemiologic research in order to present the key elements pertaining to the design and interpretation of an epidemiologic study on EDCs. The conduct of observational studies on EDCs derives from a thoughtful research question, which will help determine the subsequent methodological choices surrounding the careful selection of the study population (including the comparison group), the adequate ascertainment of exposure(s) and outcome(s) of interest, and the application of methodological and statistical concepts more specific to epidemiology. The interpretation of epidemiologic results may be arduous due to the latency occurring between EDC exposure and certain outcome(s), the complexity in capturing EDC exposure(s), and traditional methodological and statistical issues that also deserve consideration (e.g., confounding, effect modification, non-monotonic responses). Moving forward, we strongly advocate for an integrative approach of expertise in the fields of epidemiology, exposure science, risk assessment and toxicology to adequately study the health risks associated with EDCs while tackling their challenges.
10.1016/j.envres.2021.111969
A Clinical Preventive Strategy Based on a Digital Tool to Improve Access to Endocrine Disruptors Exposure Prevention: The MEDPREVED Study.
International journal of environmental research and public health
: The digitalized PREVED (PREgnancy, PreVention, Endocrine Disruptor) questionnaire was used in the clinical practices of health professionals (HP) who adhered to the MEDPREVED strategy. The objectives were to assess the strategy and to determine if it could improve access to endocrine disruptor (ED) exposure prevention. : After having filled in the digital questionnaire in HP waiting rooms, patients were invited to talk about ED exposure during the consultation. HPs were previously trained in ED and had received a prevention kit for their patients. After the seven-month implementation phase, the evaluation phase consisted of five mixed assessments: interviews with: (i) patients who were young children's parents; (ii) patients in the general population; (iii) paediatricians; (iv) midwives; and a quantitative study on GPs. Assessment concerned feasibility, accessibility, and usefulness of the strategy; we then used the Levesque model to evaluate how it could improve access to ED exposure prevention. : The study included 69 participants. The strategy appeared feasible for the filling-out step due to digital and environment access. However, it depended on patient and HP profiles. The strategy seemed useful insofar as it facilitated reflexive investment, an intention to healthy behaviour and, rather rarely, talk about ED exposure. The beginning of this discussion depended on time, prioritizing of the topic and HP profile. The strategy has confirmed the Levesque model's limiting factors and levers to access ED prevention. : The MEDPREVED strategy is feasible, accessible, and useful in clinical prevention practice. Further study is needed to measure the impact on knowledge, risk perception and behavior of beneficiaries of the MEDPREVED strategy in the medium and long term.
10.3390/ijerph191911993
Co-exposure to environmental endocrine disruptors in the US population.
Chen Lin,Luo Kai,Etzel Ruth,Zhang Xiaoyu,Tian Ying,Zhang Jun
Environmental science and pollution research international
Exposure to environmental endocrine disruptors (EEDs) has been linked to adverse health outcomes. The vast majority of studies examined one class of EEDs at a time but humans often are exposed to multiple EEDs at the same time. It is, therefore, important to know the co-exposure status of multiple EEDs in an individual, to preclude and control for potential confounding effects posed by co-exposed EEDs. This study examined the concentrations of seven classes of EEDs in the US population utilizing the data from the National Health and Nutrition Examination Survey (NHANES), 2009-2014 survey cycles. We applied linear correlation and cluster analysis to characterize the correlation profile and cluster patterns of these EEDs. We found that EEDs with a similar structure are often highly correlated. Among between-class correlations, mercury and perfluoroalkyl substances (PFAS) and cadmium and polycyclic aromatic hydrocarbons (PAHs) were two significantly correlated EEDs. In epidemiologic studies, measurement and control for co-exposure to pollutants, especially those with similar biological effects, are critical when attempting to make causal inferences. Appropriate statistical methods to handle within- and between-class correlations are needed.
10.1007/s11356-018-04105-x
Long-term stability of several endocrine disruptors in the first morning urine samples and their associations with lifestyle characteristics.
The Science of the total environment
Parabens, triclosan (TCS), bisphenols, benzophenones, and phthalates are typical endocrine disruptors (EDs) with short half-lives in the human body. The concentration levels of those EDs in a spot urine sample are frequently used in exposure assessment studies, and the reproducibility of urinary levels of these nonpersistent EDs should be considered. In the present study, we consecutively collected 45-day first morning void (FMV) urine samples, as well as daily questionnaires, in six recruited participants and measured the urinary concentrations of six parabens, TCS, nine bisphenols, five benzophenones, and ten phthalate metabolites by using high-performance liquid chromatography-tandem mass spectrometry. MeP, EtP, PrP, TCS, BPA, BPS, BPF, and most phthalate metabolites were frequently detected (over 62 % of samples). The intraclass correlation coefficients (ICCs) for ED concentrations in FMV urine samples ranged from fair to excellent for MeP (0.683), EtP (0.702), BPA (0.505), BPS (0.908), BPF (0.887), BP-3 (0.712), mMP (0.661), mEP (0.523), mBP (0.500), miBP (0.724), mBzP (0.961) and all metabolites of DEHP (0.867-0.957), whereas they were low for PrP (0.321) and TCS (0.306). After creatinine adjustment, the values of ICCs for most target EDs were increased with mild to significant improvement. The stability of ED concentrations was affected by daily diet (MeP, TCS, BPA, mMP, miBP, mBP and mBzP), food containers (PrP and mECPP), use of personal care products (HMWP metabolites), pharmaceuticals (EtP) and recorded activities (BPS, mEHP, mBzP, mEHHP and mEOHP), as confirmed by a general linear mixed model. Furthermore, extending the FMV sampling period improved the probability of acceptable reproducibility (ICCs > 0.40) of MeP, EtP, BP-3 and mEP concentrations. For BPS, BPF and HMWP metabolite concentrations showed high probabilities (>80 %) of acceptable reproducibility in the last three days, and the increasing sample size slowly improved the ability to discriminate the subjects. The results were exactly the opposite for BPA concentrations.
10.1016/j.scitotenv.2022.157873
The association between environmental endocrine disruptors and cardiovascular diseases: A systematic review and meta-analysis.
Fu Xiangjun,Xu Jie,Zhang Renyi,Yu Jie
Environmental research
BACKGROUND:Except for known cardiovascular risk factors, long-term exposure to environmental endocrine disruptors (EEDs) - a class of exogenous chemicals, or a mixture of chemicals, that can interfere with any aspect of hormone action - has been shown to increase the risk of cardiovascular diseases (CVDs), which are still controversial. OBJECTIVE:To conduct a comprehensive systematic review and meta-analysis to estimate the association between EEDs, including nonylphenol (NP), bisphenol A (BPA), polychlorinated biphenyl (PCB), organo-chlorine pesticide (OCP) and phthalate (PAE) exposure and CVD risk. METHODS:The heterogeneity between different studies was qualitatively and quantitatively evaluated using Q test and I statistical magnitude, respectively. Subgroup analysis was performed using chemical homologs - a previously unused grouping method - to extract data and perform meta-analysis to assess their exposure to CVD. RESULTS:Twenty-nine literatures were enrolled with a total sample size of 88891. The results indicated that exposure to PCB138 and PCB153 were the risk factors for CVD morbidity (odds ratio (OR) = 1.35, 95% confidence interval (CI): 1.10-1.66; OR = 1.35, 95% CI: 1.13-1.62). Exposure to organo-chlorine pesticide (OCP) (OR = 1.12, 95% CI: 1.00-1.24), as well as with phthalate (PAE) (OR = 1.11, 95% CI: 1.06-1.17) and BPA (OR = 1.19, 95% CI: 1.03-1.37) were positively associated with CVD risk, respectively. BPA exposure concentration had no correlation with total cholesterol (TC), or low-density lipoprotein (LDL), but exhibited a correlation with gender, waist circumference (WC), high-density lipoprotein (HDL), age, and body mass index (BMI) (standardized mean difference (SMD)) = 1.51; 95% CI: =(1.01-2.25); SMD = 0.16; 95% CI: (0.08-0.23); SMD = -0.19; 95% CI: (-0.27-0.12); SMD = -0.78; 95% CI: (-1.42-0.14); SMD = 0.08; 95% CI: (0.00-0.16). CONCLUSIONS:EED exposure is a risk factor for CVD. Long-term exposure to EEDs can influence cardiovascular health in humans. A possible synergistic effect may exist between the homologs. The mechanism of which needs to be further explored and demonstrated by additional prospective cohort studies, results of in vitro and in vivo analyses, as well as indices affecting CVD.
10.1016/j.envres.2020.109464
Effects on Puberty of Nutrition-Mediated Endocrine Disruptors Employed in Agriculture.
Sakali Anastasia Konstantina,Bargiota Alexandra,Fatouros Ioannis G,Jamurtas Athanasios,Macut Djuro,Mastorakos George,Papagianni Maria
Nutrients
Pesticide residues are largely found in daily consumed food because of their extensive use in farming and their long half-life, which prolongs their presence in the environment. Many of these pesticides act as endocrine-disrupting chemicals after pre- or postnatal exposure, significantly affecting, among other things, the time of puberty onset, progression, and completion. In humans, precocious or delayed puberty, and early or delayed sexual maturation, may entail several negative long-term health implications. In this review, we summarize the current evidence on the impact of endocrine-disrupting pesticides upon the timing of the landmarks of female and male puberty in both animals (vaginal opening, first estrus, and balanopreputial separation) and humans (thelarche, menarche, gonadarche). Moreover, we explore the possible mechanisms of action of the reviewed endocrine-disrupting pesticides on the human reproductive system. Access to safe, healthy, and nutritious food is fundamental for the maintenance of health and wellbeing. Eliminating the presence of hazardous chemicals in largely consumed food products may increase their nutritional value and be proven beneficial for overall health. Consequently, understanding the effects of human exposure to hazardous endocrine-disrupting pesticides, and legislating against their circulation, are of major importance for the protection of health in vulnerable populations, such as children and adolescents.
10.3390/nu13114184
Endocrine disruptors of sex hormone activities.
Molecular and cellular endocrinology
Sex hormones, such as androgens, estrogens and progestins are naturally occurring compounds that tightly regulate endocrine systems in a variety of living organisms. Uncontrolled environmental exposure to these hormones or their biological and synthetic mimetics has been widely documented. Furthermore, water contaminants penetrate soil to affect flora, fauna and ultimately humans. Because endocrine systems evolved to respond to very small changes in hormone levels, the low levels found in the environment cannot be ignored. The combined actions of sex hormones with glucocorticoids and other nuclear receptors disruptors creates additional level of complexity including the newly described "dynamic assisted loading" mechanism. We reviewed the extensive literature pertaining to world-wide detection of these disruptors and created a detailed Table on the development and current status of methods used for their analysis.
10.1016/j.mce.2021.111415
Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis.
Frontiers in endocrinology
Menarche is the first occurrence of menstrual bleeding and one of the most important events of female puberty. Alarmingly, over the last several decades, the mean age at menarche (AAM) has decreased. Environmental endocrine disruptors (EEDs) are chemicals that may interfere with the endocrine system, resulting in adverse developmental, immunological, neurological, and reproductive effects in humans. Thus, the effects of EEDs on fertility and reproduction are growing concerns in modern societies. In this study, we aimed to determine the influence of genetic and environmental factors on AAM. We used data from an AAM genome-wide association study of 329,345 women to conduct a transcriptome-wide association study (TWAS) with FUSION software. As references, we determined the gene-expression levels in the hypothalamus, pituitary gland, ovaries, uterus, and whole blood. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significantly dysregulated genes identified by the TWAS. Using the STRING database, we also generated a protein-protein-interaction network to analyze common AAM-specific genes identified by the TWAS with different tissues. We performed chemical-related gene set enrichment analysis (CGSEA) and identified significant TWAS genes to uncover relationships between different chemicals and AAM. The TWAS identified 9,848 genes; among these, 1580 genes were significant ( < 0.05), and 11 genes were significant among the hypothalamus, pituitary, ovary, uterus, and whole blood. CGSEA identified 1,634 chemicals, including 120 chemicals significantly correlated with AAM. In summary, we performed a TWAS (for genetic factors) and CGSEA (for environmental factors) focusing on AAM and identified several AAM-associated genes and EEDs. The results of this study expand our understanding of genetic and environmental factors related to the onset of female puberty.
10.3389/fendo.2022.836527
Effects of endocrine disruptors on fetal testis development, male puberty, and transition age.
Cargnelutti Francesco,Di Nisio Andrea,Pallotti Francesco,Sabovic Iva,Spaziani Matteo,Tarsitano Maria Grazia,Paoli Donatella,Foresta Carlo
Endocrine
PURPOSE:Endocrine disruptors (EDs) are exogenous substances able to impair endocrine system; consequently, they may cause numerous adverse effects. Over the last years, particular focus has been given to their harmful effects on reproductive system, but very little is known, especially in males. The aim of this review is to discuss the detrimental effects of EDs exposure on fetal testis development, male puberty, and transition age. METHODS:A search for the existing literature focusing on the impact of EDs on fetal testis development, male puberty, andrological parameters (anogenital distance, penile length, and testicular volume), and testicular cancer with particular regard to pubertal age provided the most current information available for this review. Human evidence-based reports were given priority over animal and in vitro experimental results. Given the paucity of available articles on this subject, all resources were given careful consideration. RESULTS:Information about the consequences associated with EDs exposure in the current literature is limited and often conflicting, due to the scarcity of human studies and their heterogeneity. CONCLUSIONS:We conclude that current evidence does not clarify the impact of EDs on human male reproductive health, although severe harmful effects had been reported in animals. Despite controversial results, overall conclusion points toward a positive association between exposure to EDs and reproductive system damage. Further long-term studies performed on wide number of subjects are necessary in order to identify damaging compounds and remove them from the environment.
10.1007/s12020-020-02436-9
Insights into the activation mechanism of human estrogen-related receptor γ by environmental endocrine disruptors.
Thouennon Erwan,Delfosse Vanessa,Bailly Rémy,Blanc Pauline,Boulahtouf Abdelhay,Grimaldi Marina,Barducci Alessandro,Bourguet William,Balaguer Patrick
Cellular and molecular life sciences : CMLS
The estrogen-related receptor γ (ERRγ, NR3B3) is a constitutively active nuclear receptor which has been proposed to act as a mediator of the low-dose effects of a number of environmental endocrine-disrupting chemicals (EDCs) such as the xenoestrogen bisphenol-A (BPA). To better characterize the ability of exogenous compounds to bind and activate ERRγ, we used a combination of cell-based, biochemical, structural and computational approaches. A purposely created stable cell line allowed for the determination of the EC50s for over 30 environmental ERRγ ligands, including previously unknown ones. Interestingly, affinity constants (Kds) of the most potent compounds measured by isothermal titration calorimetry were in the 50-500 nM range, in agreement with their receptor activation potencies. Crystallographic analysis of the interaction between the ERRγ ligand-binding domain (LBD) and compounds of the bisphenol, alkylphenol and naphthol families revealed a partially shared binding mode and minimal alterations of the receptor conformation upon ligand binding. Further biophysical characterizations coupled to molecular dynamics simulations suggested a mechanism through which ERRγ ligands would exhibit their agonistic properties by preserving the transcriptionally active form of the receptor while rigidifying some loop regions with associated functions. This unique mechanism contrasts with the classical one involving a ligand-induced repositioning and stabilization of the C-terminal activation helix H12.
10.1007/s00018-019-03129-x
The role of epigenetics in the reproductive toxicity of environmental endocrine disruptors.
Shi Yanbin,Qi Wen,Xu Qi,Wang Zheng,Cao Xiaolian,Zhou Liting,Ye Lin
Environmental and molecular mutagenesis
Environmental endocrine disruptors (EEDs) seriously endanger human health by interfering with the normal function of reproductive systems. In males, EEDs can affect sperm formation and semen quality as well spermatogenesis, ultimately reducing fertility. In females, EEDs can affect uterine development and the expression levels of reproduction-related genes, ultimately reducing female fertility and the normal development of the fetus. There are a large number of putative mechanisms by which EEDs can induce reproductive toxicity, and many studies have shown the involvement of epigenetics. In this review, we summarize the role of DNA methylation, noncoding RNAs, genomic imprinting, chromatin remodeling and histone modification in the reproductive toxicity of EEDs.
10.1002/em.22414
The epigenetic impacts of endocrine disruptors on female reproduction across generations†.
Rattan Saniya,Flaws Jodi A
Biology of reproduction
Humans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic dose responses that are atypical of standard toxicant exposures. The female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures.
10.1093/biolre/ioz081
A preliminary study on the relationship between environmental endocrine disruptors and precocious puberty in girls.
Journal of pediatric endocrinology & metabolism : JPEM
OBJECTIVES:To explore the associations of environmental endocrine disruptors on precocious puberty in girls. METHODS:This was a case-control study in which 30 girls with precocious puberty and 46 age- and race-matched prepubertal females were enrolled. The concentrations of 10 environment endocrine disruptors (bisphenol A, bisphenol B, butylparaben, propylparaben, ethvlparaben, methylparaben, mono-butyl phthalate, mono-2-ethylhexyl phthalate, monoethyl phthalate, and monomethyl phthalate) in urine and 10 steroid hormones (dihydrotestosterone, corticosterone, hydrocortisone, 11-deoxycortisol, 17α-hydroxy progesterone, 4-androstene-3,17-dione, estrone, deoxycorticosterone, pregnenolone, and dehydroepiandrosterone) in serum were detected with the liquid chromatography-mass spectrometry (LC-MS). RESULTS:According to the Mann-Whitney U test, urinary levels of bisphenol A, monobutyl phthalate, and monomethyl phthalate were significantly higher in the precocious group than in the prepubertal group, and blood levels of hydrocortisone, 11-deoxycortisol, corticosterone, deoxycorticosterone, and pregnenolone were significantly lower in the precocious group than in the prepubertal group (p<0.05, VIP>1). CONCLUSIONS:Our findings confirm the association between phthalate exposure and the incidence of precocious puberty in girls. Control and reduction of children exposure to phthalate esters should be considered as a health priority.
10.1515/jpem-2021-0691
Nutritional interventions to ameliorate the effect of endocrine disruptors on human reproductive health: A semi-structured review from FIGO.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
BACKGROUND:Endocrine disrupting chemicals have harmful effects on reproductive, perinatal, and obstetric outcomes. OBJECTIVE:To analyze the evidence on nutritional interventions to reduce the negative effects of endocrine disruptors on reproductive, perinatal, and obstetric outcomes. SEARCH STRATEGY:A search of MEDLINE (PubMed), Allied Health Literature (CINAHL), EMBASE, Web of Science, and the Cochrane Database was conducted from inception to May 2021. SELECTION CRITERIA:Experimental studies on human populations. DATA COLLECTION AND ANALYSIS:Data were collected from eligible studies. Risk of bias assessment was completed using the Cochrane risk of bias tool and the ROBINS-I Tool. RESULTS:Database searches yielded 15 362 articles. Removing 11 181 duplicates, 4181 articles underwent abstract screening, 26 articles were eligible for full manuscript review, and 16 met full inclusion criteria. Several interventions were found to be effective in reducing exposure to endocrine disruptors: avoidance of plastic containers, bottles, and packaging; avoidance of canned food/beverages; consumption of fresh and organic food; avoidance of fast/processed foods; and supplementation with vitamin C, iodine, and folic acid. There were some interventional studies examining therapies to improve clinical outcomes related to endocrine disruptors. CONCLUSION:Dietary alterations can reduce exposure to endocrine disruptors, with limited data on interventions to improve endocrine-disruptor-related clinical outcomes. This review provides useful instruction to women, their families, healthcare providers, and regulatory bodies.
10.1002/ijgo.14126