RESUMEN
Human health effects can arise from unregulated manual disassembly of electronic waste (e-waste) and/or hydraulic fracturing fluid spills. There is limited literature on the effects of e-waste and hydraulic fracturing wastewater exposure on the male reproductive system. Thus, this proof-of-concept study begins to address the question of how wastewater from two potentially hazardous environmental processes could affect sperm quality. Therefore, three groups of eight-week-old adult mice were exposed (5 d/wk for 6 wks) via a mealworm (Tenebrio molitor and Zophabas morio) feeding route to either: (1) e-waste leachate (50% dilution) from the Alaba Market (Lagos, Nigeria); (2) West Virginia hydraulic fracturing flowback (HFF) fluid (50% dilution); or, (3) deionized water (control). At 24-hours (hr), 3 weeks (wk), or 9-wk following the 6-wk exposure period, cohorts of mice were necropsied and adverse effects/persistence on the male reproductive system were examined. Ingestion of e-waste leachate or HFF fluid decreased number and concentration of sperm and increased both chromatin damage and numbers of morphological abnormalities in the sperm when compared to control mice. Levels of serum testosterone were reduced post-exposure (3- and 9-wk) in mice exposed to e-waste leachate and HFF when compared to time-matched controls, indicating the long-term persistence of adverse effects, well after the end of exposure. These data suggest that men living around or working in vicinity of either e-waste or hydraulic fracturing could face harmful effects to their reproductive health. From both a human health and economic standpoint, development of prevention and intervention strategies that are culturally relevant and economically sensitive are critically needed to reduce exposure to e-waste and HFF-associated toxic contaminants.
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Residuos Electrónicos , Fracking Hidráulico , Contaminantes Químicos del Agua , Masculino , Humanos , Animales , Ratones , Residuos Electrónicos/efectos adversos , Aguas Residuales/toxicidad , Nigeria , Semen/química , Genitales Masculinos , Contaminantes Químicos del Agua/toxicidadRESUMEN
Nickel oxide nanoparticles (NiO NPs) have been the focus of many toxicity studies. However, acute toxicity studies that identify toxicological dose descriptors, such as an LC50 or LD50, are lacking. In this paper, the acute toxicity of NiO NPs was evaluated in albino-derived Sprague-Dawley rats through OECD guideline studies conducted by both the oral and inhalation routes of exposure. The animals were assessed for mortality, body weight, behavioral observations, and gross necropsy. Results from previously conducted (unpublished) acute inhalation studies with larger NiO microparticles (MPs) are also included for comparison. Mortality, the primary endpoint in acute toxicity studies, was not observed for rats exposed to NiO NPs via either the oral or inhalation exposure routes, with a determined LD50 of >5000 mg/kg and an LC50 > 5.42 mg/L, respectively. Our results suggest that these NiO NPs do not exhibit serious acute toxicity in rats or warrant an acute toxicity classification under the current GHS classification criteria. This aligns with similar results for NiO MPs from this and previously published studies.
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Although there is rising global concern over the environmental, ecological, and human health risks associated with the discharge of leachates from e-waste dumpsites into the aquatic ecosystems, little is known in this research area. Thus, for this study, we first defined the chemistry of the test leachate, followed by assessment of the leachate on the development of a model aquatic organism (Fundulus heteroclitus) used extensively as a bioassay organism in pollution studies. Chemical analyses revealed that levels of phosphate (20.03 mg/L), cadmium (Cd) (0.4 mg/L), lead (Pb) (0.2 mg/L), and chromium (Cr) (0.4 mg/L) were higher than the 2009 US EPA and the 2009 National Environmental Standards and Regulations Enforcement Agency (NESREA) permissible limits. Polycyclic aromatic hydrocarbon (PAH) burdens were dominated mainly by the high molecular weight congeners, specifically the ∑4rings (73 µg/L). Total polychlorinated biphenyls (PCB) levels ranged from 0.00 to 0.40 µg/L with the ∑deca PCBs reaching the highest concentration. For the biological studies, F. heteroclitus embryos (48-h post-fertilization) were divided randomly into groups and exposed to one of six e-waste leachate concentrations (10, 1, 0.1, 0.01, 0.001, 0.0001%). Significant differences (p ≤ 0.05) between treated and control groups were observed in standard and total length, and head size. Further analysis using Duncan's post-hoc test of multiple comparison also revealed specific differences within and between specific treatment groups. We conclude that e-waste leachate arising from indiscriminate dumping into aquatic ecosystems in Nigeria contains mixtures of toxic constituents that can threaten ecosystem and public health.
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A novel, highly soluble biotin salt, magnesium biotinate (MgB), was assessed for general and genetic toxicity using several toxicologic tests. This battery of tests included in vitro bacterial reverse mutation test, in vitro mammalian micronucleus assay, and oral acute, 14-day, and 90-day repeat-dose toxicity in Sprague-Dawley (SD) rats. The results of the in vitro studies indicate that MgB is not mutagenic, clastogenic, or aneugenic. The acute oral toxicity study established an LD50 ≥ 5000 mg MgB/kg. In the 14-day oral toxicity study, doses of MgB up to 2500 mg MgB/kg/day produced no clinical signs or mortality. In the 90-day oral toxicity study, administration of 600 mg MgB/kg/day resulted in no clinical signs and was determined to be the no-observed-adverse-effect-level (NOAEL), which equates to 39 g biotin/day for a 70 kg human. Since MgB is composed of 93% biotin, the 600 mg NOAEL equates to approximately 1.3 million times the current recommended daily allowance of 30 µg biotin/day and 3900 times supplement levels of 10 mg biotin/day. Based on the toxicologic profile and lack of findings in various in vitro and in vivo studies, MgB may be considered safe for long-term human use.
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Biotina/toxicidad , Administración Oral , Animales , Biotina/administración & dosificación , Biotina/química , Línea Celular , Cricetulus , Femenino , Dosificación Letal Mediana , Magnesio/química , Masculino , Nivel sin Efectos Adversos Observados , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Pruebas de Toxicidad SubcrónicaRESUMEN
Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring: risk factors for the progression of NAFLD to cirrhosis in adults remain elusive. Buccal cavity 'painting' of pregnant mice with gutkha began on gestational days (GD) 2-4 and continued until parturition. Beginning at 12 weeks of age, a subset of offspring were transitioned to a high-fat diet (HFD). Results demonstrated that prenatal exposure to gutkha followed by an HFD in adulthood significantly increased the histologic evidence of fatty liver disease only in adult male offspring. Changes in hepatic fibrosis-related cytokines (interleukin (IL)-1b and IL-6) and in hepatic collagen mRNA expression were observed when comparing adult male offspring exposed to gutkha in utero to those not exposed. These findings indicate that maternal use of gutkha during pregnancy affects NAFLD in adult offspring in a sex-dependent manner.
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Enfermedad del Hígado Graso no Alcohólico , Efectos Tardíos de la Exposición Prenatal , Tabaco sin Humo , Animales , Colágeno , Citocinas , Dieta Alta en Grasa , Femenino , Hígado/fisiopatología , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Embarazo , Tabaco sin Humo/toxicidadRESUMEN
Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer-binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARγ (peroxisome proliferator-activated receptor γ) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.
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Aerosoles/farmacología , Sistemas Electrónicos de Liberación de Nicotina , Efectos Tardíos de la Exposición Prenatal/patología , Factores Sexuales , Animales , Femenino , Pulmón/efectos de los fármacos , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/patología , Ratones , Nicotina/farmacología , EmbarazoRESUMEN
BACKGROUND: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE: The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS: Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n=8-10 per group) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16mg/mL nicotine (+Nic). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. RESULTS: Adult offspring of both sexes exposed to +Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNγ) in the diencephalon, as well as lower levels of hippocampal IFNγ (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. DISCUSSION: These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.
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Sistemas Electrónicos de Liberación de Nicotina , Inflamación/inmunología , Locomoción/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/psicología , Estrés Psicológico/psicología , Aerosoles/análisis , Animales , Modelos Animales de Enfermedad , Femenino , Glicerol/efectos adversos , Inflamación/inducido químicamente , Ratones , Nicotina/efectos adversos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Propilenglicol/efectos adversos , Distribución Aleatoria , Estrés Psicológico/inducido químicamenteRESUMEN
Accumulating evidence indicates the developing central nervous system (CNS) is a target of air pollution toxicity. Epidemiological reports increasingly demonstrate that exposure to the particulate matter (PM) fraction of air pollution during neurodevelopment is associated with an increased risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). These observations are supported by animal studies demonstrating prenatal exposure to concentrated ambient PM induces neuropathologies characteristic of ASD, including ventriculomegaly and aberrant corpus callosum (CC) myelination. Given the role of the CC and cerebellum in ASD etiology, this study tested whether prenatal exposure to concentrated ambient particles (CAPs) produced pathological features in offspring CC and cerebella consistent with ASD. Analysis of cerebellar myelin density revealed male-specific hypermyelination in CAPs-exposed offspring at postnatal days (PNDs) 11-15 without alteration of cerebellar area. Atomic absorption spectroscopy (AAS) revealed elevated iron (Fe) in the cerebellum of CAPs-exposed female offspring at PNDs 11-15, which connects with previously observed elevated Fe in the female CC. The presence of Fe inclusions, along with aluminum (Al) and silicon (Si) inclusions, were confirmed at nanoscale resolution in the CC along with ultrastructural myelin sheath damage. Furthermore, RNAseq and gene ontology (GO) enrichment analyses revealed cerebellar gene expression was significantly affected by sex and prenatal CAPs exposure with significant enrichment in inflammation and transmembrane transport processes that could underlie observed myelin and metal pathologies. Overall, this study highlights the ability of PM exposure to disrupt myelinogenesis and elucidates novel molecular targets of PM-induced developmental neurotoxicity.
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Contaminación del Aire/efectos adversos , Cerebelo/efectos de los fármacos , Cerebelo/patología , Hierro/análisis , Material Particulado/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Animales , Cuerpo Calloso/efectos de los fármacos , Cuerpo Calloso/patología , Femenino , Masculino , Ratones , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , EmbarazoRESUMEN
The circulating pattern of immunoreactive relaxin and progestagens based on monthly and gestational stage (early, mid, late) profiles were determined during pregnancies that resulted in live calves (LIVE, nâ¯=â¯30), stillbirths (STILLB, nâ¯=â¯3), abortions (ABORT, nâ¯=â¯5) and presumptive false pregnancies (FALSE, nâ¯=â¯8), and during the follicular (nâ¯=â¯34) and luteal phase (nâ¯=â¯58). Monthly LIVE relaxin concentrations steadily increased during gestation, but values did not significantly exceed those of the luteal phase until 9â¯months prior to parturition, peaking during the final month at 2356â¯ng/ml. Relaxin surged (Pâ¯<â¯0.05) during the final week of gestation (36,397â¯ng/ml), undergoing a 3 and 9-fold increase compared with concentrations in the preceding two weeks, respectively. Monthly relaxin production did not differ among each reproductive state with the exception of months-13-16 where concentrations were higher (Pâ¯<â¯0.001) for STILLB than LIVE. Relaxin concentration was reduced (Pâ¯<â¯0.0001) by 849% in placental versus maternal serum collected within 1â¯day of labor. Mid- and late-pregnancy progestagen concentrations were lower for FALSE (Pâ¯<â¯0.001) compared with STILLB and LIVE. Late pregnancy progestagen concentrations were reduced for FALSE (Pâ¯<â¯0.05) and ABORT (Pâ¯<â¯0.02) compared with LIVE and STILLB. Monthly progestagen production in ABORT tended to be lower than LIVE across a range of gestational months (Months 2, 7, 8, 11) but this difference only became significant during months 14 and 15. Results indicate that relaxin is primarily produced by the CL during pregnancy, and that concentrations could not be used to differentiate from non-pregnant females until the final 6â¯months of gestation. In addition, as would be expected from a primarily CL product, relaxin cannot be used to detect abnormal pregnancies. Conversely, progestagens, which are produced by both the placenta and CL can be used to differentiate FALSE from normal pregnancy and may be useful indicators of fetal health in the killer whale.
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Pérdida del Embrión/sangre , Preñez/sangre , Progestinas/sangre , Relaxina/sangre , Orca/sangre , Animales , Femenino , Parto/sangre , Circulación Placentaria , Embarazo , Progesterona/sangre , Reproducibilidad de los Resultados , ReproducciónRESUMEN
Approximately 1 million women smoke during pregnancy despite evidence demonstrating serious juvenile and/or adult diseases being linked to early-life exposure to cigarette smoke. Susceptibility could be determined by factors in previous generations, that is, prenatal or "maternal" exposures to toxins. Prenatal exposure to airborne pollutants such as mainstream cigarette smoke has been shown to induce early-life insults (i.e., gene changes) in Offspring that serve as biomarkers for disease later in life. In this investigation, we have evaluated genome-wide changes in the lungs of mouse Dams and their juvenile Offspring exposed prenatally to mainstream cigarette smoke. An additional lung model was tested alongside the murine model, as a means to find an alternative in vitro, human tissue-based replacement for the use of animals in medical research. Our toxicogenomic and bio-informatic results indicated that in utero exposure altered the genetic patterns of the fetus, which could put them at greater risk for developing a range of chronic illnesses in later life. The genes altered in the in vitro, cell culture model were reflected in the murine model of prenatal exposure to mainstream cigarette smoke. The use of alternative in vitro models derived from human medical waste tissues could be viable options to achieve human endpoint data and conduct research that meets the remits for scientists to undertake the 3Rs practices.
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Accumulating studies indicate that the brain is a direct target of air pollution exposure during the fetal period. We have previously demonstrated that exposure to concentrated ambient particles (CAPs) during gestation produces ventriculomegaly, periventricular hypermyelination, and enlargement of the corpus callosum (CC) during postnatal development in mice. This study aimed to further characterize the cellular basis of the observed hypermyelination and determine if this outcome, among other effects, persisted as the brain matured. Analysis of CC-1+ mature oligodendrocytes in the CC at postnatal days (PNDs) 11-15 suggest a premature maturational shift in number and proportion of total cells in prenatally CAPs-exposed males and females, with no overall change in total CC cellularity. The overall number of Olig2+ lineage cells in the CC was not affected in either sex at the same postnatal timepoint. Assessment of myelin status at early brain maturity (PNDs 57-61) revealed persistent hypermyelination in CAPs-exposed animals of both sexes. In addition, ventriculomegaly was persistent in CAPs-treated females, with possible amelioration of ventriculomegaly in CAPs-exposed males. When oligodendrocyte precursor cell (OPC) pool status was analyzed at PNDs 57-61, there were significant CAPs-induced alterations in cycling Ki67+/Olig2+ cell number and proportion of total cells in the female CC. Total CC cellularity was slightly elevated in CAPs-exposed males at PNDs 57-61. Overall, these data support a growing body of evidence that demonstrate the vulnerability of the developing brain to environmental insults such as ambient particulate matter. The sensitivity of oligodendrocytes and myelin, in particular, to such an insult warrants further investigation into the mechanistic underpinnings of OPC and myelin disruption by constituent air pollutants.
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Vaina de Mielina/efectos de los fármacos , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Material Particulado/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Hidrocefalia/inducido químicamente , Hidrocefalia/fisiopatología , Masculino , Ratones , Tamaño de la Partícula , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Factores SexualesRESUMEN
Exposure to fine ambient particulates (PM2.5) during gestation or neonatally has potent neurotoxic effects. While biological and behavioral data indicate a vulnerability to environmental pollutants across distinct neurodevelopmental windows, the behavioral consequences following exposure across the entire developmental period remain unknown. Moreover, several epidemiological studies support a link between developmental exposure to air pollution and an increased risk of later receiving a diagnosis of autism spectrum disorders (ASD), a neurodevelopmental disorder that persists throughout life. In the current study we sought to determine whether perinatal exposure to PM2.5 would reduce sociability and increase repetitive deficits in mice, two hallmark characteristics of ASD. Pregnant female B6C3F1 mice were exposed daily to concentrated ambient PM2.5 (CAPs) (135.8µg/m3) or filtered air (3.1µg/m3) throughout gestation followed by additional exposures to both dams and their litters from days 2-10 postpartum. Adult offspring were subsequently assessed for social and repetitive behaviors at 20 weeks of age. Daily perinatal exposure to CAPs significantly decreased sociability in male and female mice as measured by the social approach task; however, reductions in reciprocal social interaction and increased grooming behavior were only present in male offspring exposed to CAPs. These findings demonstrate that exposure to particulate air pollutants throughout early neurodevelopment induces long lasting behavioral deficits in a sex-dependent manner and may be an underlying cause of neurodevelopmental disorders such as ASD.
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Trastorno Autístico/inducido químicamente , Trastorno Autístico/psicología , Aseo Animal , Exposición Materna , Material Particulado/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/psicología , Conducta Social , Animales , Femenino , Masculino , Ratones , Tamaño de la Partícula , EmbarazoRESUMEN
In the seminal plasma of terrestrial mammalian species known as induced (e.g., camels) and spontaneous (e.g., cattle) ovulators, an ovulation-inducing factor (OIF) with a protein structure similar to beta-nerve growth factor (ß-NGF) has been identified. Detection of an OIF/NGF in the seminal plasma of cetaceans would have both basic and applied implications in reproductive biology and conservation management programs. A preliminary evaluation was conducted to characterize the distribution and abundance of seminal plasma proteins in aquarium-based belugas and a Pacific white-sided and bottlenose dolphin. Initially, SDS-PAGE was used with 50 µg of total protein for separation; thereafter, Western immunoblot was used with anti-NGF. In addition to odontocete seminal plasma, a purified fraction of llama seminal plasma (100 ng protein) and an extract of mouse brain (20 µg total protein) were included as positive controls for NGF. Within the two belugas, visual inspection of the protein bands indicated similar distribution and intensity. However, among the belugas and Pacific white-sided and bottlenose dolphins there was more diversity than similarity in the distribution and abundance of seminal plasma proteins. While immunoreactivity of NGF was distinctly evident in the llama and mouse positive controls, there was no visual reactivity in any of the odontocete samples. These preliminary results provide novel information indicating more homogeneity within and heterogeneity among seminal plasma proteins of ondentocetes. Although NGF was not immunologically detected, future studies are required to address the apparent limitations of immuno-detection of NGF, especially if the post-translational form of ß-NGF is in low abundance in the seminal plasma of belugas and Pacific white-sided and bottlenose dolphins.
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BACKGROUND: Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative. OBJECTIVES: Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW. METHODS: For the first study, timed-pregnant B6C3F1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.55.5; 2: GD6.514.5; 3: GD14.516.5; 4: GD0.516.5) aligning to milestones during human development. RESULTS: In the first experiment, exposure to 160 µg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (â¼1.1 wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 µg/m3 for periods 14, respectively). Pregnancy was significantly shortened (vs. FA) by â¼0.4d when exposure occurred during gestational periods 2 and 4, and by â¼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by â¼10% compared with FA, and placental weight was reduced (â¼8%) on GD17.5 if exposure occurred only during period 3. CONCLUSIONS: Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029.
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Contaminantes Atmosféricos/toxicidad , Recién Nacido de Bajo Peso , Exposición por Inhalación , Exposición Materna , Material Particulado/toxicidad , Nacimiento Prematuro/inducido químicamente , Animales , Peso al Nacer/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Tamaño de la Partícula , Embarazo , Factores de TiempoRESUMEN
Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 µm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 µg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations.
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Contaminantes Atmosféricos/toxicidad , Encéfalo/efectos de los fármacos , Trastornos del Neurodesarrollo/inducido químicamente , Material Particulado/toxicidad , Efectos Tardíos de la Exposición Prenatal/etiología , Animales , Encéfalo/embriología , Encéfalo/patología , Femenino , Edad Gestacional , Masculino , Ratones , Trastornos del Neurodesarrollo/patología , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/patologíaRESUMEN
This study was conducted to critically evaluate weekly and monthly circulating concentrations of immunoreactive relaxin throughout pregnancies that resulted in live births, stillbirths, and abortions in aquarium-based bottlenose dolphins. A relaxin RIA was used to analyze serum collected during 74 pregnancies involving 41 dolphins and 8 estrous cycles as well as 8 non-pregnant dolphins. Pregnancies resulted in live births (n=60), stillbirths (n=7), or abortions (n=7). Relative to parturition (Month 0), monthly changes (P<0.0001) in relaxin was indicated by relatively low concentrations during early pregnancy (Months -12 to -9) which subsequently increased (P<0.05) during mid- (Months -8 to -5) to late (Months -4 to -1) pregnancy; relaxin was highest (P<0.05) at the time of parturition. Post-parturition (Month 1), concentrations decreased (P<0.05). During the first 4weeks post-ovulation, relaxin concentrations were not different between pregnant and non-pregnant dolphins (status-by-week interaction, P=0.59). Status-by-month interaction (P<0.0002) involving different pregnancy outcomes was due, impart, to an increase in relaxin during early pregnancy (P<0.05) that was comparable among dolphins with live births, stillbirths, and abortions except concentrations were lower (P<0.05; 52%) at mid-pregnancy in association with pregnancy loss. Thereafter, concentrations increased (P<0.05) during late pregnancy in dolphins with stillbirths but not in dolphins with abortions. In conclusion, this study provided new information on the pregnancy-specific nature of relaxin, critical evaluation of the fundamental characteristics of relaxin during pregnancy and pregnancy loss, and clarification on the strengths and limitations of relaxin as a diagnostic aid to determine pregnancy status and assess maternal-fetal health in bottlenose dolphins.
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Aborto Veterinario/sangre , Delfín Mular/fisiología , Preñez , Relaxina/sangre , Mortinato/veterinaria , Animales , Delfín Mular/sangre , Femenino , Parto/fisiología , Embarazo , Resultado del Embarazo/veterinaria , Preñez/sangre , Preñez/fisiologíaRESUMEN
Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 µg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations.
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Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/congénito , Compuestos de Cadmio/toxicidad , Nanopartículas/toxicidad , Óxidos/toxicidad , Lesión Renal Aguda/patología , Proteínas de Fase Aguda/biosíntesis , Proteínas de Fase Aguda/genética , Animales , Animales Recién Nacidos , Biomarcadores/orina , Compuestos de Cadmio/farmacocinética , Creatinina/orina , Femenino , Glucosuria/inducido químicamente , Glucosuria/orina , Receptor Celular 1 del Virus de la Hepatitis A , Exposición por Inhalación , Riñón/patología , Lipocalina 2 , Lipocalinas/biosíntesis , Lipocalinas/genética , Glándulas Mamarias Animales/metabolismo , Exposición Materna , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Ratones , Proteínas Oncogénicas/biosíntesis , Proteínas Oncogénicas/genética , Óxidos/farmacocinética , Embarazo , ARN Mensajero/biosíntesisRESUMEN
CONTEXT: Cadmium oxide nanoparticles (CdO NPs) are employed in optoelectronic devices and as a starting material for generating quantum dots as well as for medical imaging and targeting of pharmaceutical agents to disease sites. However, there are lack of data concerning short- and long-term effects of CdO NPs on the lungs. OBJECTIVE: To determine the effects of inhaled CdO NPs at an occupationally relevant concentration on pulmonary injury and repair, and on systemic immunity in adult male mice. METHODS: Mice were exposed to 240 µg CdO NPs/m(3) for seven days (3 h/d) and lavage levels of pulmonary injury/inflammatory markers, bacterial uptake by circulating phagocytes, and lung histology examined either one or seven days following the final exposure. RESULTS: Levels of total protein, lactate dehydrogenase activity, cytokine markers of inflammation (i.e. interleukin-1ß, tumor necrosis factor-α, and interferon-γ), tissue remodeling matrix metalloproteinases (MMP)-2 and -9 activity, and phagocytic activity of circulating phagocytes were significantly increased one day after the final exposure. By seven days post-exposure, MMP-2 activity decreased to control levels, while MMP-9 activity remained significantly above control values, although dropping by about half from day one. CONCLUSIONS: This study demonstrates that short-term inhalation exposure to CdO NPs can stimulate pathways in the lungs associated with inflammation, cell injury, and tissue remodeling as well as alter immune function. Findings here demonstrate that even short-term inhalation exposure to CdO NPs in the workplace could lead to deleterious pulmonary effects in exposed workers.
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Compuestos de Cadmio/toxicidad , Lesión Pulmonar/inducido químicamente , Nanopartículas del Metal/toxicidad , Óxidos/toxicidad , Neumonía/inducido químicamente , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Citocinas/inmunología , Modelos Animales de Enfermedad , Escherichia coli , L-Lactato Deshidrogenasa/inmunología , Recuento de Leucocitos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Lesión Pulmonar/inmunología , Lesión Pulmonar/patología , Masculino , Metaloproteinasa 2 de la Matriz/inmunología , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Fagocitosis/efectos de los fármacos , Neumonía/inmunología , Neumonía/patologíaRESUMEN
The popularity of smokeless tobacco (ST) is growing rapidly and its prevalence of use is rising globally. Consumption of Gutkha, an addictive form of ST, is particularly common amongst South Asian communities throughout the World. This includes within the US, following large-scale immigration into the country. However, there exists a lack of knowledge concerning these alternative tobacco products. To this end, a study was carried out to determine the toxicity of gutkha, and what role, if any, nicotine contributes to the effects. Adult male mice were treated daily for 3-week (5 day/week, once/day), via the oral mucosa, with equal volumes (50 µL) of either sterile water (control), a solution of nicotine dissolved in water (0.24 mg of nicotine), or a solution of lyophilized guthka dissolved in water (21 mg lyophilized gutkha). Serum cotinine, measured weekly, was 36 and 48 ng/mL in gutkha- and nicotine-treated mice, respectively. Results demonstrated that exposure to nicotine and gutkha reduced heart weight, while exposure to gutkha, but not nicotine, decreased liver weight, body weight, and serum testosterone levels (compared to controls). These findings suggest that short-term guhtka use adversely impacts growth and circulating testosterone levels, and that gutkha toxicity may be driven by components other than nicotine. As use of guthka increases worldwide, future studies are needed to further delineate toxicological implications such that appropriate policy decisions can be made.
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Tabaco sin Humo/toxicidad , Animales , Hidrocarburo de Aril Hidroxilasas/metabolismo , Peso Corporal/efectos de los fármacos , Cotinina/sangre , Citocromo P-450 CYP2A6 , Corazón/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Tamaño de los Órganos/efectos de los fármacos , Testosterona/sangre , Nicotiana , Pruebas de ToxicidadRESUMEN
One industrially important metal oxide nanoparticle (NP) is cadmium oxide (CdO). A study was performed using timed-pregnant CD-1 mice to determine if Cd associated with inhaled CdO NP could reach the placenta and adversely affect the developing fetus and/or neonate. Pregnant mice were exposed by inhalation either every other day to 100 µg of freshly generated CdO/m(3) (exposure 1) or daily to 230 µg CdO/m(3) (exposure 2). In each exposure, mice were exposed to CdO NP or carrier gas (control) for 2.5 h from 4.5 days post coitus (dpc) through 16.5 dpc. At 17.5 dpc, fetuses and placentas from both exposures 1 and 2 were collected, measured, and weighed. A subgroup from the second exposure was allowed to give birth, and neonates were weighed daily until weaning. Cadmium in the uterus and placenta, as well as in other maternal organs, was elevated in NP-treated mice, but was undetectable in fetuses at 17.5 dpc. Daily inhalation of 230 µg CdO NP/m(3) decreased the incidence of pregnancy (i.e., no evidence of implantation) by 23%, delayed maternal weight gain, altered placental weight, and decreased fetal length, as well as delayed neonatal growth. This study demonstrates that inhalation of CdO NP during pregnancy adversely affects reproductive fecundity and alters fetal and postnatal growth of the developing offspring.