Prepubertal oral exposure to relevant doses of acrylamide impairs the testicular antioxidant system in adulthood, increasing protein carbonylation and lipid peroxidation.

The increased prevalence of human infertility due to male reproductive disorders has been linked to extensive exposure to chemical endocrine disruptors. Acrylamide (AA) is a compound formed spontaneously during the thermal processing of some foods that are mainly consumed by children and adolescents. We previously found that prepubertal exposure to AA causes reduced sperm production and functionality. Oxidative stress is recognized as the main cause of reduced sperm quality and quantity. In this sense, our objective was to evaluate the expression and activity of genes related to enzymatic antioxidant defense, nonprotein thiols, lipid peroxidation (LPO), protein carbonylation (PC) and DNA damage in the testes of rats exposed to acrylamide (2.5 or 5 mg/kg) from weaning to adult life by gavage. For the AA2.5 and AA5 groups, there were no alterations in the transcript expression of genes related to enzymatic antioxidant defense. The enzymatic activities and metabolic parameters were also not affected in the AA2.5 group. For the AA5 group, the enzymatic activities of G6PDH and GPX were reduced, SOD was increased, and protein carbonylation (PC) was increased. Data were also evaluated by Integrate Biomarker Response (IBRv2), a method to analyze and summarize the effects on biomarkers between doses. The IBRv2 index was calculated as 8.9 and 18.71 for AA2.5 and AA5, respectively. The following biomarkers were affected by AA2.5: decreased enzymatic activities of G6PDH, SOD, and GPX, increased GST and GSH, increased LPO and PC, and decreased DNA damage. For AA5, decreased enzymatic activities of G6PDH, GST, CAT and GPX, increased SOD and GSH, increased PC, and decreased LPO and DNA damage were observed. In conclusion, AA exposure during the prepubertal period causes imbalances in the testicular enzymatic antioxidant defense, contributing to the altered spermatic scenario in the testes of these rats.

Epigenetic Regulation in Exposome-Induced Tumorigenesis: Emerging Roles of ncRNAs.

Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with our unique characteristics such as genetics, physiology, and epigenetics. Epigenetics investigates modifications in the expression of genes that do not depend on the underlying DNA sequence. Some studies have confirmed that environmental factors may promote disease in individuals or subsequent progeny through epigenetic alterations. Variations in the epigenetic machinery cause a spectrum of different disorders since these mechanisms are more sensitive to the environment than the genome, due to the inherent reversible nature of the epigenetic landscape. Several epigenetic mechanisms, including modifications in DNA (e.g., methylation), histones, and noncoding RNAs can change genome expression under the exogenous influence. Notably, the role of long noncoding RNAs in epigenetic processes has not been well explored in the context of exposome-induced tumorigenesis. In the present review, our scope is to provide relevant evidence indicating that epigenetic alterations mediate those detrimental effects caused by exposure to environmental toxicants, focusing mainly on a multi-step regulation by diverse noncoding RNAs subtypes.

Total tin (TSn) biomagnification: Evaluating organotin trophic flow and dispersion using hepatic TSn concentrations and stable isotope (C, N) data of nektonic organisms from Brazil.

A previous investigation of our research team has demonstrated the suitability of using hepatic total tin (ΣSn) concentrations for evaluating dolphin exposure to organotins (OTs). The present study develops the previous technique into three different approaches that comprise data: (1) on hepatic ΣSn concentrations of 121 Guiana dolphins (Sotalia guianensis) from five different coastal areas (CAs): (2) on ΣSn, δ13C and δ15N for 40 dolphins from Rio de Janeiro state (RJ), including ten different delphinid species; as well as (3) on hepatic ΣSn concentrations and δ15N values on 31 individuals from five different fish species from Sepetiba Bay (SB, Rio de Janeiro-RJ, Brazil). Hepatic ΣSn concentrations of Guiana dolphins from Guanabara Bay (GB, RJ) were significantly higher than those found in other four CAs from S and SE Brazilian regions. Significant positive correlations were found between ΣSn concentrations and δ13C data in delphinid species, demonstrating a coast-ocean gradient in dolphin exposure to OTs in RJ state. Significant and positive correlations were observed between ΣSn concentrations and both δ15N and Trophic Position (TP) values of fish, as well as high values were found for Trophic Magnification Factor (TMF = 3.03) and Trophic Magnification Slope (TMS = 0.14), demonstrating OT biomagnification in SB ichthyofauna.

Environmental toxins and the impact of other endocrine disrupting chemicals in women's reproductive health.

This review aimed to look into agents and mechanisms characterized as endocrine disrupting chemicals (EDCs). These agents are known to cause several harmful effects to the reproductive system of women and wildlife. There is a wide range of chemicals, developed for commercial use mainly in agriculture, which may cause endocrine disruption. Numerous studies show evidence of environmental contamination. However, no one is being held liable for the damages. The most important potentially harmful agents are identified and described, along with the different effects they have on the female genital area. Brazil is a large consumer of pesticides and others chemicals that may interfere with a normal women's life. We analyzed and described the mode of action and the impacts of different EDCs (bisphenols, phthalates, atrazine, polychlorinated and polybrominated biphenyls, DDT-dichlorodiphenyltrichloroethane; DDE-dichlorodiphenyldichloroethylene; DDD-dichlorodiphenyldichloroethane; and DES-diethylstilbestrol) on the genital area, ovarian steroidogenesis, polycystic ovary syndrome, endometriosis, the structure of the uterus and the vagina, and on the formation of leiomyomas.

Analysis of Toxic and Essential Elements in the Blood and Feathers of Humboldt Penguins ( Spheniscus humboldti) at Punta San Juan, Peru.

Whole blood, serum, and feather samples from 29 Humboldt Penguins ( Spheniscus humboldti) at the Punta San Juan Marine Protected Area, Peru, were analyzed for 55 toxic and essential elements by using inductively coupled plasma mass spectrometry. Mercury (Hg) was analyzed by cold vapor atomic fluorescence. Maximum Hg concentrations in serum (0.0056 mg/g), whole blood (0.297 mg/kg), and feathers (1.8 mg/kg dry weight) were at levels generally not considered to cause health impairment. Of the elements analyzed, only eight (aluminum, calcium, iron, Hg, potassium, magnesium, sodium, and zinc) were detected in serum. These elements, plus selenium and titanium, were also quantifiable in whole blood. Feather analysis detected quantifiable values for the elements found in serum, plus arsenic, boron, barium, copper, manganese, and titanium. Results indicate this important breeding population of endangered penguins did not appear to be exposed to environmental elemental contaminants at levels detrimental to health and reproductive success. However, identification of measurable concentrations of toxic elements at low levels underscores the need for continued environmental monitoring, particularly in the face of expanding regional human populations and industrial growth. These results provide important reference data for temporospatial monitoring of this and other penguin populations.

ASSESSMENT OF POLYCHLORINATED BIPHENYLS, ORGANOCHLORINE PESTICIDES, AND POLYBROMINATED DIPHENYL ETHERS IN THE BLOOD OF HUMBOLDT PENGUINS ( SPHENISCUS HUMBOLDTI) FROM THE PUNTA SAN JUAN MARINE PROTECTED AREA, PERU.

Persistent organic pollutants were assessed in Humboldt Penguins ( Spheniscus humboldti) from the Punta San Juan Marine Protected Area, Peru, in the austral winter of 2009. Plasma samples from 29 penguins were evaluated for 31 polychlorinated biphenyl (PCB) congeners and 11 organochlorine pesticides (OCPs) by using gas chromatography coupled to an ion trap mass spectrometer and for 15 polybrominated diphenyl ether (PBDE) congeners by using gas chromatography coupled with high-resolution mass spectrometry. The detection rate for PCBs in the samples was 69%, with congeners 105, 118, 180, and 153 most commonly detected. The maximum ΣPCB concentration was 25 ng/g. The detection rate for DDT, DDD, and/or DDE was higher than for other OCP residues (90%; maximum concentration=10 ng/g). The detection rate for PBDEs was 86%, but most concentrations were low (maximum ΣPBDE concentration=3.81 ng/g). This crucial breeding population of S. humboldti was not exposed to contaminants at levels detrimental to health and reproductive success; however, the identified concentrations of legacy and recently emerged toxicants underscore the need for temporal monitoring and diligence to protect this endangered species in the face of regional human population and industrial growth. These results also provide key reference values for spatial comparisons throughout the range of this species.

Modified mycotoxins: An updated review on their formation, detection, occurrence, and toxic effects.

Modified mycotoxins are metabolites that normally remain undetected during the testing for parent mycotoxin. These modified forms of mycotoxins can be produced by fungi or generated as part of the defense mechanism of the infected plant. In some cases, they are formed during food processing. The various processing steps greatly affect mycotoxin levels present in the final product (free and modified), although the results are still controversial regarding the increase or reduction of these levels, being strongly related to the type of process and the composition of the food in question. Evidence exists that some modified mycotoxins can be converted into the parent mycotoxin during digestion in humans and animals, potentially leading to adverse health effects. Some of these formed compounds can be even more toxic, in case they have higher bioaccessibility and bioavailability than the parent mycotoxin. The modified mycotoxins can occur simultaneously with the free mycotoxin, and, in some cases, the concentration of modified mycotoxins may exceed the level of free mycotoxin in processed foods. Even though toxicological data are scarce, the possibility of modified mycotoxin conversion to its free form may result in a potential risk to human and animal health. This review aims to update information on the formation, detection, occurrence, and toxic effects caused by modified mycotoxin.

Acute regulation of multidrug resistance-associated protein 2 localization and activity by cAMP and estradiol-17ß-D-glucuronide in rat intestine and Caco-2 cells.

Multidrug resistance-associated protein 2 (MRP2) is an ATP-dependent transporter expressed at the brush border membrane of the enterocyte that confers protection against absorption of toxicants from foods or bile. Acute, short-term regulation of intestinal MRP2 activity involving changes in its apical membrane localization was poorly explored. We evaluated the effects of dibutyryl-cAMP (db-cAMP), a permeable analog of cAMP, and estradiol-17ß-D-glucuronide (E217G), an endogenous derivative of estradiol, on MRP2 localization and activity using isolated rat intestinal sacs and Caco-2 cells, a model of human intestinal epithelium. Changes in MRP2 localization were studied by Western blotting of plasma membrane (PM) vs. intracellular membrane (IM) fractions in both experimental models, and additionally, by confocal microscopy in Caco-2 cells. After 30 min of exposure, db-cAMP-stimulated sorting of MRP2 from IM to PM both in rat jejunum and Caco-2 cells at 10 and 100 µM concentrations, respectively, with increased excretion of the model substrate 2,4-dinitrophenyl-S-glutathione. In contrast, E217G (400 µM) induced internalization of MRP2 together with impairment of transport activity. Confocal microscopy analysis performed in Caco-2 cells confirmed Western blot results. In the particular case of E217G, MRP2 exhibited an unusual pattern of staining compatible with endocytic vesiculation. Use of selective inhibitors demonstrated the participation of cAMP-dependent protein kinase and classic calcium-dependent protein kinase C in db-cAMP and E217G effects, respectively. We conclude that localization of MRP2 in intestine may be subjected to a dynamic equilibrium between plasma membrane and intracellular domains, thus allowing for rapid regulation of MRP2 function.

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood.

Prenatal exposure to neurotoxicants such as lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However, few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ HumanMethylation450 assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an in vitro human embryonic stem cell model of Pb exposure. We model Pb exposure-associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. For our study, we randomly selected umbilical cord blood from 24 male and 24 female children from the 1st and 4th quartiles of Pb levels. Our data show that Pb-associated changes in the 5hmC and 5mC profiles can be divided into sex-dependent and sex-independent categories. Interestingly, differential 5mC sites are better markers of Pb-associated sex-dependent changes compared to differential 5hmC sites. In this study we identified several 5hmC and 5mC genomic loci, which we believe might have some potential as early biomarkers of prenatal Pb exposure.

Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children.

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8-13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8-13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.