Exposure to environmental chemicals and perinatal psychopathology.

Women are nearly twice as likely to develop mood disorders compared with men, and incidence is greatest during reproductive transitions, including pregnancy and postpartum. Because these periods are characterized by dramatic hormonal and physiologic changes, there is heightened susceptibility to external factors, such as exposure to environmental toxicants, which may play a role in maternal psychopathology. The purpose of this scoping review was to provide an overview of studies conducted in humans and animal models on the effects of nonoccupational exposure to environmental chemicals on maternal psychopathology during the perinatal period. The largest number of studies examined exposure to environmental tobacco smoke and antenatal depression and showed consistently positive findings, although more prospective studies using biomarkers for exposure assessment are needed. The few studies examining persistent organic pollutants such as polybrominated diphenyl ethers and perinatal depression were consistent in showing associations with increased depressive symptoms. Results were mixed for exposure to heavy metals and non-persistent chemicals, but a strong literature in animal models supported an association between bisphenols and phthalates and reduced maternal behavior and care of pups after parturition. Biological mechanisms may include endocrine disruption, neurotransmitter system impairment, alterations in gene expression, and immune activation and inflammation. Additional longitudinal studies that include biospecimen collection are essential to furthering the understanding of how environmental toxicants during pregnancy may affect perinatal psychopathology and the underlying mechanisms of action. Future work should also leverage the parallels between animal and human maternal behavior, thereby highlighting the opportunity for multidisciplinary work in this avenue.

On Placental Toxicology Studies and Cerium Dioxide Nanoparticles.

The human placenta is a transient organ essential for pregnancy maintenance, fetal development and growth. It has several functions, including that of a selective barrier against pathogens and xenobiotics from maternal blood. However, some pollutants can accumulate in the placenta or pass through with possible repercussions on pregnancy outcomes. Cerium dioxide nanoparticles (CeO2 NPs), also termed nanoceria, are an emerging pollutant whose impact on pregnancy is starting to be defined. CeO2 NPs are already used in different fields for industrial and commercial applications and have even been proposed for some biomedical applications. Since 2010, nanoceria have been subject to priority monitoring by the Organization for Economic Co-operation and Development in order to assess their toxicity. This review aims to summarize the current methods and models used for toxicology studies on the placental barrier, from the basic ones to the very latest, as well as to overview the most recent knowledge of the impact of CeO2 NPs on human health, and more specifically during the sensitive window of pregnancy. Further research is needed to highlight the relationship between environmental exposure to CeO2 and placental dysfunction with its implications for pregnancy outcome.

Perspective on prenatal polychlorinated biphenyl exposure and the development of the progeny nervous system (Review).

The developmental origins of health and disease concept illustrates that exposure in early life to various factors may affect the offspring's long­term susceptibility to disease. During development, the nervous system is sensitive and vulnerable to the environmental insults. Polychlorinated biphenyls (PCBs), which are divided into dioxin­like (DL­PCBs) and non­dioxin­like PCBs (NDL­PCBs), are synthetic persistent environmental endocrine­disrupting chemicals. The toxicological mechanisms of DL­PCBs have been associated with the activation of the aryl hydrocarbon receptor and NDL­PCBs have been associated with ryanodine receptor­mediated calcium ion channels, which affect neuronal migration, promote dendritic growth and alter neuronal connectivity. In addition, PCB accumulation in the placenta destroys the fetal placental unit and affects endocrine function, particularly thyroid hormones and the dopaminergic system, leading to neuroendocrine disorders. However, epidemiological investigations have not achieved a consistent result in different study cohorts. The present review summarizes the epidemiological differences and possible mechanisms of the effects of intrauterine PCB exposure on neurological development.

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome.

Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1ß secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca2+-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2-/- mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.

Skeletal pathology and bone mineral density changes in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) inhabiting arsenic polluted areas of Yellowknife, Northwest Territories (Canada): A radiographic densitometry study.

The City of Yellowknife is a known hotspot of arsenic contamination and there is a growing body of evidence suggesting that local wildlife in the vicinity of the abandoned Giant Mine site may be at risk of decreased bone mineralization and various bone disorders. The purpose of this study was to preliminarily measure bone mineral density (BMD) changes and investigate the incidence, pattern, and severity of bone lesions in wild muskrats and red squirrels breeding in three (3) catchment areas at different distances from the Giant Mine Site in Yellowknife, Northwest Territories (Canada): ~2 km (location 1), ~18 km (location 2), and ~40-100 km (location 3). Full femoral bones of 15 muskrats and 15 red squirrels were collected from the three sampling locations (5 from each location) and subjected to radiographic analysis and densitometric measurements. The patterns and severities of bone lesions, including changes in bone mineral density, were evaluated and compared between groups. As levels were significantly higher in the bones of muskrats caught from location 1 and 2, relative to location 3. Further, As and Cd levels were significantly higher in the bones of squirrels caught from locations 1 and 2 relative to squirrels caught from location 3. The preliminary results from bones revealed that radiographic abnormalities such as bone rarefaction, osteopenia, and thinning of the femoral shafts with significant ossific cystic lesions and bowing were the most common skeletal pathologies found in bones of red squirrels from the three locations. Radiographic appearances of massive sclerosis and dysplasia, including severe osteocondensation and osteopathia striata-like abnormalities, were found in the bones of muskrats from all the sampling locations. Densitometric evaluation showed no significant differences between the three locations in the bone parameters measured. However, there was a statistically significant correlation between As content in the bones of muskrats and percent fat content in the femur samples, which suggests that accumulation of As could have been a causal factor for a change in percent fat in femurs of muskrats.

Evaluation of telomere length and genotoxicity among asphalt associated workers.

There are contradictory reports about bitumen exposure and malignancy risk worldwide. Also, the evidence for genotoxicity risk among workers occupationally exposed to asphalt is insufficient. The study intended to evaluate particulate matter 10 (PM10) at the workplace and biomarkers of genotoxicity effects among a group of asphalt workers in and around Bangalore, India. This study involved a total of 107 participants (54 exposed group and 53 unexposed control group). To evaluate the genotoxicity, the urinary 8-OHdG and relative telomere length as oxidative damage while micronucleus (MN) assay for cytogenetic damage was carried out during the study. The majority of workers have reported health complaints and 57.4% of them were not using any personal protective equipments (PPE's). The level of PM10 detected was 104 ± 9.5 µg/m3 and 619 ± 22.7 µg/m3 in the road paving and asphalt mixing sites respectively. The biomonitoring study observed a highly significant (p = <0.001) increase in the level of 8-hydroxy-2-deoxyguanosine (8-OHdG) in the exposed group (23.17 ± 8.65 ng/mg creatinine) compared to the control (13.6 ± 7.12 ng/mg creatinine), revealed age significant associated and non-smoking borderline significant associated for oxidative stress. The relative telomere length (TL) analysis revealed its highly significant (p = 0.004) reduction in the exposed group, adjusted mean 0.95 (95% CI 0.83-1.07) compared to the control 1.06 (95% CI 0.91-1.26). The job category (p = 0.028), non-smoking (p = 0.026), and tobacco chewing (p = 0.013) were associated with reduced relative TL in the asphalt exposed group. In cytogenotoxicity analysis, the mean micronucleus (MN) frequency per 100 cells in the exposed group (26.46 ± 19.8) was significantly (p = <0.001) increased over the control group (8.56 ± 7.18). Neither smoking habit nor age appeared to influence the MN frequencies in either group. In the present study, we have demonstrated genetic damage in workers occupationally exposed to asphalt and particulate matter, raising concern for an increased risk of malignancy in these workers.

Commercial and Industrial Chemical Hazards for Ruminants: An Update.

Livestock can be exposed to a wide variety of commercial or industrial chemicals that have variable toxicity. Adverse effects can be due to acute or chronic illnesses and deaths or due to contamination of meat or milk intended for human consumption. A diagnosis can be challenging in the absence of a known exposure. It is critical that a complete evaluation be conducted and appropriate samples be collected for possible analysis. Appropriate experts and regulatory agencies should be consulted as soon as possible to avoid potential contaminated animal products reaching consumers.

Protective Effect of Grape and Apple Juices against Cadmium Intoxication in the Kidney of Rats.

BACKGROUND: The objective of this study was to evaluate protective effect of grape and apple juices against toxicity induced by cadmium in the kidney of rats. METHODS: A total of 20 male-Wistar rats were distributed into four groups (n=5): Control group: animals received an intraperitoneal (i.p.) injection of 0.9% saline solution and after 15 days, 1 mL of water was administered for 15 days, via gavage; Cadmium group: animals received an intraperitoneal injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1 mL of water was administered for 15 days via gavage; Cadmium+Grape Juice: animals received an i.p. injection of cadmium chloride (1.2 mg/kg), and after 15 days, 0.8 mL of grape juice was administered for 15 days, via gavage; Cadmium+Apple Juice: animals received i.p. injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1.0 mL of apple juice was administered for 15 days, via gavage. RESULTS: Histopathological analysis revealed severe tubular lesion and necrosis in the group exposed to cadmium, while animals exposed to grape or apple juices showed a significant reduction of tissue injury. 8-OHdG immunoexpression, DNA damage, cytochrome C and catalase gene expressions and Toll like signaling pathway (TLR2, and pIKKα/ß) decreased in animals treated with grape juice when compared to cadmium group. CONCLUSION: Taken together, we conclude that grape and apple juices had a protective effect by means of antioxidant, antigenotoxic actions and for promoting tissue regeneration in the kidney of rats following cadmium intoxication.

Lead Poisoning and Intelligence: A Search for Cause and Effect in the Scottish Mental Surveys.

In 1932 and again in 1947, the Scottish Council for Research in Education conducted the Scottish Mental Surveys. Testing two cohorts, one in 1932 and another in 1947, researchers set out to measure-using the same validated test each time-the intelligence of every Scottish child 11 years of age. The stated impetus for the Surveys was a fear that average Scottish intelligence was declining. But when investigators compared the results of the 1947 Survey with those from 1932 their predictions were completely upended. Instead of average intelligence declining, it had risen, substantially. The author argues that based on a study of the relevant ecosystems in place in Scotland at the time the increase in intelligence resulted from a decline in lead body burden. There is no evidence that the children were tested for lead. The decline is thought to have closely followed a fall in occupational lead use, a heightened awareness of the dangers of lead-solvency, improvements in lead plumbing in working-class homes, and a national campaign to improve the nutrition of women and children. Evidence shows that milk consumption in Scotland increased sharply, especially among children, beginning in the mid-1930s, just prior to and following the birth of the second cohort. This provided a source of calcium in a diet that had shown signs of deficiency. Evidence also suggests that lead contamination, from lead water pipes and industrial sources, was widely prevalent in Scotland in the early part of the twentieth century.

Assessment of Endothelial Dysfunction with Methylated Arginines and L-arginine in Cadmium-Exposed People: a Pilot Study.

BACKGROUND: Workers can be exposed to cadmium (Cd) in various industries. On the other hand, another potential source for Cd exposure is the food chain and smoking. Environmental pollution to Cd plays an important role in the development of atherosclerosis. Asymmetric dimethyl arginine (ADMA) levels promote the development of endothelial dysfunction and atherosclerosis-related diseases such as hypertension, acute coronary syndrome, congestive heart failure, and peripheral vascular diseases. The aim of this study is to evaluate the cardiovascular risks of non-symptomatic cadmium-exposed workers and to promote the value of methylated arginines in screening of toxic exposures. METHODS: A total 176 participants were included in the study which has been separated as control group (n = 79) and Cd-exposed group (n = 94). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for toxicological analysis of Cd levels. Also, liquid Chromatography-Mass Spectrometry (LC-MS/MS) was used for levels of methylated arginines such as ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl-L-arginine (L-NM-MA), homoarginine, and citrulline. RESULTS: Statistically significant differences were observed for control and Cd-exposed groups, respectively as follows: Cd levels (0.25 ± 0.13 µg/L and 1.33 ± 0.61 µg/L), ADMA (0.16 ± 0.04 µmol/L and 0.22 ± 0.11 µmol/L), SDMA (0.21 ± 0.06 µmol/L and 0.27 ± 0.07 µmol/L), L-NMMA(0.02 ± 0.01 µmol/L and 0.03 ± 0.01µmol/L), and arginine/ADMA levels (695.82 ± 620.63 and 478.30 ± 432.61). CONCLUSIONS: Our results suggest that workers chronically exposed to Cd showed imbalances in endothelial parameters.

Association between the persistent organic pollutants and polycystic ovary syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: Current evidence concerning the association between persistent organic pollutants (POPs) and polycystic ovary syndrome (PCOS) is inconsistent. The aim of the present systematic review and meta-analysis is to evaluate the role of POPs in PCOS. METHODS: Databases including PubMed, Embase, Web of Science, and CNKI will be searched to identify qualified studies. All qualified studies regarding the association between POPs and PCOS will be included. The primary outcome of the present study is POPs levels in serum of subjects. Pooled analysis with corresponding 95% confidence intervals will be performed. RESULTS: The comprehensive analysis and quantitative assessment will provide a better understanding of POPs concentrations in patients with PCOS. CONCLUSION: This meta-analysis and systematic review will generate evidence of the association between POPs and PCOS. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019126373.

"Bisphenol a: an emerging threat to male fertility".

BACKGROUND: Among the factors causing male infertility, one of the most debated is the exposure to environmental contaminants. Recently, the chemical compound Bisphenol A (BPA) has drawn attention from the reproductive science community, due to its ubiquitous presence in day-to-day life. Its toxic action appears to mainly affect the male reproductive system, directly impacting male fertility. MAIN: The purpose of this review is to investigate current research data on BPA, providing an overview of the findings obtained from studies in animal and human models, as well as on its supposed mechanisms of action. CONCLUSION: A clear understanding of BPA action mechanisms, as well as the presumed risks deriving from its exposure, is becoming crucial to preserve male fertility. The development and validation of methodologies to detect BPA toxic effects on reproductive organs can provide greater awareness of the potential threat that this chemical represents.

Ambient temperature and pesticide poisoning: a time-series analysis.

Limited studies have explored the association between ambient temperature and the disease burden of pesticide poisoning. Our study aims to estimate associations between daily mean temperature and pesticide poisoning incidence with lag effect. A distributed lag nonlinear model with Poisson distribution was used to examine the nonlinear lagged effects of ambient temperature on pesticide poisoning incidence. Overall, the estimated effects of temperature on pesticide poisoning incidence were non-linear, with higher relative risks (RRs) at hotter temperatures. It was found that the high temperature had acute and short-term effects and then declined rapidly along the lag days with the maximum risk occurring 0 day of exposure. Considering the 5-day cumulative RR for daily mean temperature, the temperature generally showed a positive association with the pesticide poisoning incidence, achieving the maximum risk at 31°C. In general, pesticide poisoning incidence increased with higher temperatures, with the strongest effects occurring shortly.

Association of In Utero Persistent Organic Pollutant Exposure With Placental Thyroid Hormones.

In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n = 28) and without (n = 30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T4, T3, and rT3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T4, T3, and rT3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T4 was inversely associated with BDEs 99, 100, ΣPBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, ΣOTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.

The references level of cadmium intake for renal dysfunction in a Chinese population.

Recent several studies indicated that a more restrictive dietary intake guideline for cadmium should be made for sufficient health protection. In the present study, we showed the references level of food cadmium intake (FCd) and total cadmium intake (TCd) for renal dysfunction by using benchmark dose (BMD) approach. 342 subjects living in a control and a cadmium polluted area were included in this study. The FCd, TCd and cadmium in urine (UCd) and blood (BCd) were calculated or determined. Urinary ß2Microglobulin (UBMG) was determined as indicator of renal function. The median FCd, TCd, UCd and BCd were 1.4 g, 1.4 g, 3.1 µg/g creatinine(cr) and 1.3 µg/L in control and 3.3 g, 3.6 g, 13.5 µg/g cr and 12.1 µg/L in polluted area. The 95% lower confidence bounds of BMD (BMDLs) of FCd for renal dysfunction were 1.36-1.55 g (BMR = 10%) and 0.88-1.11 g (BMR = 5%). The BMDLs of TCd were 1.29-1.46 g (BMR = 10%) and 0.73-0.95 g (BMR = 5%). FCd and TCd are valuable markers for the predication of renal dysfunction induced by cadmium. The BMDLs of FCd were close to previous report in Japan and the BMDLs of TCd were lower than the critical standard previously reported, in particular at BMR of 5% which can be interpreted as representing the influence of smoking.

Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective.

The kidney consists of numerous cell types organized into the nephron, which is the basic functional unit of the kidney. Any stimuli that induce loss of these cells can induce kidney damage and renal failure. The cause of renal failure can be intrinsic or extrinsic. Extrinsic causes include cardiovascular disease, obesity, diabetes, sepsis, and lung and liver failure. Intrinsic causes include glomerular nephritis, polycystic kidney disease, renal fibrosis, tubular cell death, and stones. The kidney plays a prominent role in mediating the toxicity of numerous drugs, environmental pollutants and natural substances. Drugs known to be nephrotoxic include several cancer therapeutics, drugs of abuse, antibiotics, and radiocontrast agents. Environmental pollutants known to target the kidney include cadmium, mercury, arsenic, lead, trichloroethylene, bromate, brominated-flame retardants, diglycolic acid, and ethylene glycol. Natural nephrotoxicants include aristolochic acids and mycotoxins such as ochratoxin, fumonisin B1, and citrinin. There are several common characteristics between mechanisms of renal failure induced by nephrotoxicants and extrinsic causes. This common ground exists primarily due to similarities in the molecular mechanisms mediating renal cell death. This review summarizes the current state of the field of nephrotoxicity. It emphasizes integrating our understanding of nephrotoxicity with pathological-induced renal failure. Such approaches are needed to address major questions in the field, which include the diagnosis, prognosis and treatment of both acute and chronic renal failure, and the progression of acute kidney injury to chronic kidney disease.

Transcriptome analysis reveals the molecular mechanism of hepatic metabolism disorder caused by chromium poisoning in chickens.

Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions. Histopathological examination and transcriptome data for chromium-poisoned livers and control livers were annotated with Illumina® HiSeq 2000. The histopathological examination in chromium poisoning groups showed diapedesis, hemolysis, degeneration, nucleus pycnosis, and central phlebectasia in the liver. A total of 334 genes were upregulated and 509 genes were downregulated. The most strongly upregulated genes were HKDC1, DDX4, ACACA, FDFT1, CYYR1, PPP1R3C, and SLC16A14, while the most downregulated genes were MYBPC3, CCKAR, PCK1, and CPT1A. A Gene Ontology (GO) term with the highest enrichment of DEGs is small molecule metabolic process. In cell component domain, the term with the highest enrichment is extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that glucose metabolism, lipid metabolism, and protein metabolism were the most important metabolic pathways in the liver. The current study first time provides important clues and evidence for identifying the differentially expressed genes in livers due to Cr (VI)-induced liver injury in chickens.

Exploring exposure to Agent Orange and increased mortality due to bladder cancer.

BACKGROUND: During the Vietnam War, many veterans were exposed to Agent Orange (AO), a chemical defoliant containing varying levels of the carcinogen dioxin. The health effects of AO exposure have been widely studied in the VA population. Here we review and interpret data regarding the association between AO exposure and bladder cancer (BC) mortality. MAIN FINDINGS: Data evaluating the association between AO and BC is limited. Methods characterizing exposure have become more sophisticated over time. Several studies support the link between AO exposure and increased mortality due to BC, including the Korean Veterans Health Study. CONCLUSIONS: Available data suggest an association with exposure to AO and increased mortality due to BC. In patients exposed to AO, increased frequency of cystoscopic surveillance and potentially more aggressive therapy for those with BC may be warranted but utility of these strategies remains to be proven. Additional research is required to better understand the relationship between AO and BC.

Cyanide poisoning of a Cooper's hawk ( Accipiter cooperii).

A Cooper's hawk ( Accipiter cooperii) was found dead in a ditch leading from a heap leach pad at a gold mine in Nevada. Observations at autopsy included an absence of external lesions, traces of subcutaneous and coronary fat, no food in the upper gastrointestinal tract, and no lesions in the viscera. Cyanide concentrations (µg/g ww) were 5.04 in blood, 3.88 in liver, and 1.79 in brain. No bacteria or viruses were isolated from tissues, and brain cholinesterase activity was within the normal range for a Cooper's hawk.

[Effects of organochloride pesticides on dyslipidemias].

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.