Experimental Evidence of 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) Transgenerational Effects on Reproductive Health.

Previous studies have demonstrated that endocrine disruptors (EDs) can promote the transgenerational inheritance of disease susceptibility. Among the many existing EDs, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) affects reproductive health, including in humans, following direct occupational exposure or environmental disasters, for instance the Agent Orange sprayed during the Vietnam War. Conversely, few studies have focused on TCDD multigenerational and transgenerational effects on human reproductive health, despite the high amount of evidence in animal models of such effects on male and female reproductive health that mimic human reproductive system disorders. Importantly, these studies show that paternal ancestral TCDD exposure substantially contributes to pregnancy outcome and fetal health, although pregnancy outcome is considered tightly related to the woman's health. In this work, we conducted a systematic review of the literature and a knowledge synthesis in order (i) to describe the findings obtained in rodent models concerning TCDD transgenerational effects on reproductive health and (ii) to discuss the epigenetic molecular alterations that might be involved in this process. As ancestral toxicant exposure cannot be changed in humans, identifying the crucial reproductive functions that are negatively affected by such exposure may help clinicians to preserve male and female fertility and to avoid adverse pregnancy outcomes.

The EDCMET Project: Metabolic Effects of Endocrine Disruptors.

Endocrine disruptors (EDs) are defined as chemicals that mimic, block, or interfere with hormones in the body's endocrine systems and have been associated with a diverse array of health issues. The concept of endocrine disruption has recently been extended to metabolic alterations that may result in diseases, such as obesity, diabetes, and fatty liver disease, and constitute an increasing health concern worldwide. However, while epidemiological and experimental data on the close association of EDs and adverse metabolic effects are mounting, predictive methods and models to evaluate the detailed mechanisms and pathways behind these observed effects are lacking, thus restricting the regulatory risk assessment of EDs. The EDCMET (Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways) project brings together systems toxicologists; experimental biologists with a thorough understanding of the molecular mechanisms of metabolic disease and comprehensive in vitro and in vivo methodological skills; and, ultimately, epidemiologists linking environmental exposure to adverse metabolic outcomes. During its 5-year journey, EDCMET aims to identify novel ED mechanisms of action, to generate (pre)validated test methods to assess the metabolic effects of Eds, and to predict emergent adverse biological phenotypes by following the adverse outcome pathway (AOP) paradigm.

Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience.

Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural origins that are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests. However, there is evidence that non-EATS modalities-and even natural sources, such as decomposition products of plants or parasitic infections-can affect vertebrate endocrine systems. Recently, the disturbance of natural circadian light rhythms by artificial light at night (ALAN) has been identified as another ED. Reviewing the knowledge about EDs affecting teleosts and amphibians leads to implications for risk assessment. The generally accepted WHO-definition for EDs, which focuses exclusively on 'exogenous substances' and neglects parasitic infections or ALAN, seems to require some adaptation. Natural EDs have been involved in coevolutionary processes for ages without resulting in a general loss of biodiversity. Therefore, to address the 'One Health'-principle, future research and regulatory efforts should focus on minimizing anthropogenic factors for endocrine disruption. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Effects of a Plastic-Free Lifestyle on Urinary Bisphenol A Levels in School-Aged Children of Southern Italy: A Pilot Study.

Bisphenol A (BPA) is an endocrine disruptor (ED) frequently used in food packaging. BPA is used as a monomer in the manufacture of some food packaging. This study aimed to evaluate the urinary BPA concentration in an Italian pediatric cohort, testing the levels of this ED over a period of 6 months, evaluating the effects of a diet regimen with a reduction of Plastic Food Packaging (PFP). One hundred thirty Italian children were enrolled and divided into two groups "School Canteen" and "No School Canteen." The first group consumed one meal at school using a plastic-free service for 5 days/weeks, while the other group did not modify their normal meal-time habits. The BPA levels were tested in urine samples at three time points: T0, is the time before the application of the plastic-free regimen diet; T3, 3 months later; and T6, 6 months later. A reduction of urine BPA levels was detected in the "School Canteen" group. In particular, the reduction was significant analyzing both the intra (among the three testing times) group and inter (between "School Canteen" and "No School Canteen") group variability. Our results show the effects of a diet regimen with a reduction of PFP, demonstrating a connection between urinary BPA levels and food packaging.

The endocrine disruptors among the environmental risk factors for stillbirth.

Persistent organic pollutants have been lately taken into consideration for their adverse effects, as possible stillbirth contributors; stillbirth can be in fact considered the most dramatic pregnancy complication. Congenital abnormalities account for few stillbirths and many related disorders are potentially modifiable or often coexist, such as maternal infections, non-communicable diseases, lifestyle factors and maternal age. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour. For this reason, many current efforts are focusing on the study of endocrine disruptor (ED) placental transfer, to better understand the in utero exposure dynamics. In this regard, our research group has investigated, by gas chromatography-mass spectrometry, the EDs presence in brain samples of 24 stillbirths, collected over a 3-year period (2012-2014), coming from the Northeast Italy, a notorious area devoted to apple cultivation. Surprisingly, organochlorine pesticides (OCPs), well-known EDs, have been detected in 11 samples. Apart from the noteworthy evidence of pesticides' bio-persistence, this finding implies a redefinition of the placental barrier concept: not a real safety system, but a time-deferral mechanism of absorption. The term 'placental barrier' in fact refers to a 4-membrane structure, made up by two epithelial layers, which exactly lining the chorionic villi, and by two endothelial layers, belonging to the feeding vessels for the fetus. It is an effective barrier only for a low administration of water-soluble substances, which encounter obstacle to cross four instead of two membranes. High doses of water-soluble compounds can reach appreciable concentration in the fetal blood, and the lipid-soluble chemicals, such as EDs, are able to pass the placental barrier, through a simple mechanism of passive diffusion, even in minimal concentrations. After crossing the placental barrier, it is emerged from our results that they can also pass through the still immature blood-brain barrier of the fetus.