Toxics

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10 pages, 2012 KiB

Open AccessCommunication

The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism

by Korawin Triyasakorn, Ubah Dominic Babah Ubah, Brandon Roan, Minsyusheen Conlin, Ken Aho and Prabha S. Awale

Toxics 2022, 10(7), 379; https://doi.org/10.3390/toxics10070379 - 09 Jul 2022

Cited by 4 | Viewed by 2174

Abstract

Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well [...] Read more.

Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well as a histone deacetylase inhibitor, and fetal exposure to VPA increases the risk of ASD. While the VPA model has been well-characterized for behavioral and neuronal deficits including hyperconnectivity, microglia, the principal immune cells of CNS that regulate dendrite and synapse formation during early brain development, have not been well-characterized and may provide potential hints regarding the etiology of this disorder. Therefore, in this study, we determined the effect of prenatal exposure to VPA on microglial numbers during early postnatal brain development. We found that prenatal exposure to VPA causes a significant reduction in the number of microglia in the primary motor cortex (PMC) during early postnatal brain development, particularly at postnatal day 6 (P6) and postnatal day 10 (P10) in male mice. The early microglial reduction in the VPA model coincides with active cortical synaptogenesis and is significant because it may potentially play a role in mediating impaired connectivity in ASD. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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25 pages, 1304 KiB

Open AccessArticle

Multi- and Transgenerational Effects of Developmental Exposure to Environmental Levels of PFAS and PFAS Mixture in Zebrafish (Danio rerio)

by Alex Haimbaugh, Chia-Chen Wu, Camille Akemann, Danielle N. Meyer, Mackenzie Connell, Mohammad Abdi, Aicha Khalaf, Destiny Johnson and Tracie R. Baker

Toxics 2022, 10(6), 334; https://doi.org/10.3390/toxics10060334 - 18 Jun 2022

Cited by 15 | Viewed by 3618

Abstract

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and are tied to myriad health effects. Despite the phasing out of the manufacturing of two types of PFASs (perfluorosulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)), chemical composition renders them effectively indestructible by [...] Read more.

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and are tied to myriad health effects. Despite the phasing out of the manufacturing of two types of PFASs (perfluorosulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)), chemical composition renders them effectively indestructible by ambient environmental processes, where they thus remain in water. Exposure via water can affect both human and aquatic wildlife. PFASs easily cross the placenta, exposing the fetus at critical windows of development. Little is known about the effects of low-level exposure during this period; even less is known about the potential for multi- and transgenerational effects. We examined the effects of ultra-low, very low, and low-level PFAS exposure (7, 70, and 700 ng/L PFOA; 24, 240, 2400 ng/L PFOS; and stepwise mixtures) from 0–5 days post-fertilization (dpf) on larval zebrafish (Danio rerio) mortality, morphology, behavior and gene expression and fecundity in adult F0 and F1 fish. As expected, environmentally relevant PFAS levels did not affect survival. Morphological abnormalities were not observed until the F1 and F2 generations. Behavior was affected differentially by each chemical and generation. Gene expression was increasingly perturbed in each generation but consistently showed lipid pathway disruption across all generations. Dysregulation of behavior and gene expression is heritable, even in larvae with no direct or indirect exposure. This is the first report of the transgenerational effects of PFOA, PFOS, and their mixture in terms of zebrafish behavior and untargeted gene expression. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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35 pages, 11678 KiB

Open AccessArticle

Developmental Neurotoxicity and Behavioral Screening in Larval Zebrafish with a Comparison to Other Published Results

by Kimberly A. Jarema, Deborah L. Hunter, Bridgett N. Hill, Jeanene K. Olin, Katy N. Britton, Matthew R. Waalkes and Stephanie Padilla

Toxics 2022, 10(5), 256; https://doi.org/10.3390/toxics10050256 - 17 May 2022

Cited by 9 | Viewed by 3037

Abstract

With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish (Danio rerio) [...] Read more.

With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish (Danio rerio) larvae using a behavioral Light/Dark assay. Larvae (n = 16–24 per concentration) were exposed to each chemical (0.0001–120 μM) during development and locomotor activity was assessed. Approximately half of the chemicals (n = 30) did not show any gross developmental toxicity (i.e., mortality, dysmorphology or non-hatching) at the highest concentration tested. Twelve of the 31 chemicals that did elicit developmental toxicity were toxic at the highest concentration only, and thirteen chemicals were developmentally toxic at concentrations of 10 µM or lower. Eleven chemicals caused behavioral effects; four chemicals (6-aminonicotinamide, cyclophosphamide, paraquat, phenobarbital) altered behavior in the absence of developmental toxicity. In addition to screening a library of chemicals for developmental neurotoxicity, we also compared our findings with previously published results for those chemicals. Our comparison revealed a general lack of standardized reporting of experimental details, and it also helped identify some chemicals that appear to be consistent positives and negatives across multiple laboratories. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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18 pages, 1207 KiB

Open AccessArticle

Chronic Perigestational Exposure to Chlorpyrifos Induces Perturbations in Gut Bacteria and Glucose and Lipid Markers in Female Rats and Their Offspring

by Narimane Djekkoun, Flore Depeint, Marion Guibourdenche, Hiba El Khayat El Sabbouri, Aurélie Corona, Larbi Rhazi, Jerome Gay-Queheillard, Leila Rouabah, Farida Hamdad, Véronique Bach, Moncef Benkhalifa and Hafida Khorsi-Cauet

Toxics 2022, 10(3), 138; https://doi.org/10.3390/toxics10030138 - 12 Mar 2022

Cited by 8 | Viewed by 2971

Abstract

An increasing burden of evidence is pointing toward pesticides as risk factors for chronic disorders such as obesity and type 2 diabetes, leading to metabolic syndrome. Our objective was to assess the impact of chlorpyrifos (CPF) on metabolic and bacteriologic markers. Female rats [...] Read more.

An increasing burden of evidence is pointing toward pesticides as risk factors for chronic disorders such as obesity and type 2 diabetes, leading to metabolic syndrome. Our objective was to assess the impact of chlorpyrifos (CPF) on metabolic and bacteriologic markers. Female rats were exposed before and during gestation and during lactation to CPF (1 mg/kg/day). Outcomes such as weight, glucose and lipid profiles, as well as disturbances in selected gut bacterial levels, were measured in both the dams (at the end of the lactation period) and in their female offspring at early adulthood (60 days of age). The results show that the weight of CPF dams were lower compared to the other groups, accompanied by an imbalance in blood glucose and lipid markers, and selected gut bacteria. Intra-uterine growth retardation, as well as metabolic disturbances and perturbation of selected gut bacteria, were also observed in their offspring, indicating both a direct effect on the dams and an indirect effect of CPF on the female offspring. Co-treatment with inulin (a prebiotic) prevented some of the outcomes of the pesticide. Further investigations could help better understand if those perturbations mimic or potentiate nutritional risk factors for metabolic syndrome through high fat diet. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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14 pages, 2125 KiB

Open AccessFeature PaperArticle

Triiodothyronine or Antioxidants Block the Inhibitory Effects of BDE-47 and BDE-49 on Axonal Growth in Rat Hippocampal Neuron-Glia Co-Cultures

by Hao Chen, Rhianna K. Carty, Adrienne C. Bautista, Keri A. Hayakawa and Pamela J. Lein

Toxics 2022, 10(2), 92; https://doi.org/10.3390/toxics10020092 - 18 Feb 2022

Cited by 3 | Viewed by 1833

Abstract

We previously demonstrated that polybrominated diphenyl ethers (PBDEs) inhibit the growth of axons in primary rat hippocampal neurons. Here, we test the hypothesis that PBDE effects on axonal morphogenesis are mediated by thyroid hormone and/or reactive oxygen species (ROS)-dependent mechanisms. Axonal growth and [...] Read more.

We previously demonstrated that polybrominated diphenyl ethers (PBDEs) inhibit the growth of axons in primary rat hippocampal neurons. Here, we test the hypothesis that PBDE effects on axonal morphogenesis are mediated by thyroid hormone and/or reactive oxygen species (ROS)-dependent mechanisms. Axonal growth and ROS were quantified in primary neuronal-glial co-cultures dissociated from neonatal rat hippocampi exposed to nM concentrations of BDE-47 or BDE-49 in the absence or presence of triiodothyronine (T3; 3–30 nM), N-acetyl-cysteine (NAC; 100 µM), or α-tocopherol (100 µM). Co-exposure to T3 or either antioxidant prevented inhibition of axonal growth in hippocampal cultures exposed to BDE-47 or BDE-49. T3 supplementation in cultures not exposed to PBDEs did not alter axonal growth. T3 did, however, prevent PBDE-induced ROS generation and alterations in mitochondrial metabolism. Collectively, our data indicate that PBDEs inhibit axonal growth via ROS-dependent mechanisms, and that T3 protects axonal growth by inhibiting PBDE-induced ROS. These observations suggest that co-exposure to endocrine disruptors that decrease TH signaling in the brain may increase vulnerability to the adverse effects of developmental PBDE exposure on axonal morphogenesis. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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22 pages, 2604 KiB

Open AccessArticle

Developmental Phenotypic and Transcriptomic Effects of Exposure to Nanomolar Levels of 4-Nonylphenol, Triclosan, and Triclocarban in Zebrafish (Danio rerio)

by Jessica Phillips, Alex S. Haimbaugh, Camille Akemann, Jeremiah N. Shields, Chia-Chen Wu, Danielle N. Meyer, Bridget B. Baker, Zoha Siddiqua, David K. Pitts and Tracie R. Baker

Toxics 2022, 10(2), 53; https://doi.org/10.3390/toxics10020053 - 24 Jan 2022

Cited by 8 | Viewed by 3754

Abstract

Triclosan, triclocarban and 4-nonylphenol are all chemicals of emerging concern found in a wide variety of consumer products that have exhibited a wide range of endocrine-disrupting effects and are present in increasing amounts in groundwater worldwide. Results of the present study indicate that [...] Read more.

Triclosan, triclocarban and 4-nonylphenol are all chemicals of emerging concern found in a wide variety of consumer products that have exhibited a wide range of endocrine-disrupting effects and are present in increasing amounts in groundwater worldwide. Results of the present study indicate that exposure to these chemicals at critical developmental periods, whether long-term or short-term in duration, leads to significant mortality, morphologic, behavioral and transcriptomic effects in zebrafish (Danio rerio). These effects range from total mortality with either long- or short-term exposure at 100 and 1000 nM of triclosan, to abnormalities in uninflated swim bladder seen with long-term exposure to triclocarban and short-term exposure to 4-nonylphenol, and cardiac edema seen with short-term 4-nonylphenol exposure. Additionally, a significant number of genes involved in neurological and cardiovascular development were differentially expressed after the exposures, as well as lipid metabolism genes and metabolic pathways after exposure to each chemical. Such changes in behavior, gene expression, and pathway abnormalities caused by these three known endocrine disruptors have the potential to impact not only the local ecosystem, but human health as well. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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20 pages, 8975 KiB

Open AccessArticle

Transgenerational Effects of Prenatal Endocrine Disruption on Reproductive and Sociosexual Behaviors in Sprague Dawley Male and Female Rats

by Bailey A. Kermath, Lindsay M. Thompson, Justin R. Jefferson, Mary H. B. Ward and Andrea C. Gore

Toxics 2022, 10(2), 47; https://doi.org/10.3390/toxics10020047 - 20 Jan 2022

Cited by 5 | Viewed by 2598

Abstract

Endocrine-disrupting chemicals (EDCs) lead to endocrine and neurobehavioral changes, particularly due to developmental exposures during gestation and early life. Moreover, intergenerational and transgenerational phenotypic changes may be induced by germline exposure (F2) and epigenetic germline transmission (F3) generation, respectively. Here, we assessed reproductive [...] Read more.

Endocrine-disrupting chemicals (EDCs) lead to endocrine and neurobehavioral changes, particularly due to developmental exposures during gestation and early life. Moreover, intergenerational and transgenerational phenotypic changes may be induced by germline exposure (F2) and epigenetic germline transmission (F3) generation, respectively. Here, we assessed reproductive and sociosexual behavioral outcomes of prenatal Aroclor 1221 (A1221), a lightly chlorinated mix of PCBs known to have weakly estrogenic mechanisms of action; estradiol benzoate (EB), a positive control; or vehicle (3% DMSO in sesame oil) in F1-, F2-, and F3-generation male and female rats. Treatment with EDCs was given on embryonic day (E) 16 and 18, and F1 offspring monitored for development and adult behavior. F2 offspring were generated by breeding with untreated rats, phenotyping of F2s was performed in adulthood, and the F3 generation were similarly produced and phenotyped. Although no effects of treatment were found on F1 or F3 development and physiology, in the F2 generation, body weight in males and uterine weight in females were increased by A1221. Mating behavior results in F1 and F2 generations showed that F1 A1221 females had a longer latency to lordosis. In males, the F2 generation showed decreased mount frequency in the EB group. In the F3 generation, numbers of ultrasonic vocalizations were decreased by EB in males, and by EB and A1221 when the sexes were combined. Finally, partner preference tests in the F3 generation revealed that naïve females preferred F3-EB over untreated males, and that naïve males preferred untreated over F3-EB or F3-A1221 males. As a whole, these results show that each generation has a unique, sex-specific behavioral phenotype due to direct or ancestral EDC exposure. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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20 pages, 3109 KiB

Open AccessArticle

Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning

by Ross Gillette, Michelle Dias, Michael P. Reilly, Lindsay M. Thompson, Norma J. Castillo, Erin L. Vasquez, David Crews and Andrea C. Gore

Toxics 2022, 10(1), 30; https://doi.org/10.3390/toxics10010030 - 11 Jan 2022

Cited by 3 | Viewed by 1982

Abstract

All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors [...] Read more.

All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors based on evidence of their vulnerability to direct or ancestral exposures, together with their importance in reproduction and survival of a species. Using a novel “two hits, three generations apart” experimental rat model, we investigated interactions of two classes of EDCs across six generations. PCBs (a weakly estrogenic mixture Aroclor 1221, 1 mg/kg), Vinclozolin (antiandrogenic, 1 mg/kg) or vehicle (6% DMSO in sesame oil) were administered to pregnant rat dams (F0) to directly expose the F1 generation, with subsequent breeding through paternal or maternal lines. A second EDC hit was given to F3 dams, thereby exposing the F4 generation, with breeding through the F6 generation. Approximately 1200 male and female rats from F1, F3, F4 and F6 generations were run through tests of sociability and social novelty as indices of social preference. We leveraged machine learning using DeepLabCut to analyze nuanced social behaviors such as nose touching with accuracy similar to a human scorer. Surprisingly, social behaviors were affected in ancestrally exposed but not directly exposed individuals, particularly females from a paternally exposed breeding lineage. Effects varied by EDC: Vinclozolin affected aspects of behavior in the F3 generation while PCBs affected both the F3 and F6 generations. Taken together, our data suggest that specific aspects of behavior are particularly vulnerable to heritable ancestral exposure of EDC contamination, that there are sex differences, and that lineage is a key factor in transgenerational outcomes. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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12 pages, 939 KiB

Open AccessArticle

Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

by Rafael R. Domingues, Hannah P. Fricke, Celeste M. Sheftel, Autumn M. Bell, Luma C. Sartori, Robbie S. J. Manuel, Chandler J. Krajco, Milo C. Wiltbank and Laura L. Hernandez

Toxics 2022, 10(1), 11; https://doi.org/10.3390/toxics10010011 - 01 Jan 2022

Cited by 11 | Viewed by 3455

Abstract

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on [...] Read more.

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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17 pages, 4594 KiB

Open AccessArticle

A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

by Jelonia T. Rumph, Kayla J. Rayford, Victoria R. Stephens, Sharareh Ameli, Pius N. Nde, Kevin G. Osteen and Kaylon L. Bruner-Tran

Toxics 2022, 10(1), 7; https://doi.org/10.3390/toxics10010007 - 27 Dec 2021

Cited by 3 | Viewed by 2623

Abstract

New bronchopulmonary dysplasia is a developmental lung disease associated with placental dysfunction and impaired alveolarization. Risk factors for new BPD include prematurity, delayed postnatal growth, the dysregulation of epithelial-to-mesenchymal transition (EMT), and parental exposure to toxicants. Our group previously reported that a history [...] Read more.

New bronchopulmonary dysplasia is a developmental lung disease associated with placental dysfunction and impaired alveolarization. Risk factors for new BPD include prematurity, delayed postnatal growth, the dysregulation of epithelial-to-mesenchymal transition (EMT), and parental exposure to toxicants. Our group previously reported that a history of paternal toxicant exposure increased the risk of prematurity and low birth weight in offspring. A history of paternal toxicant exposure also increased the offspring’s risk of new BPD and disease severity was increased in offspring who additionally received a supplemental formula diet, which has also been linked to poor lung development. Risk factors associated with new BPD are well-defined, but it is unclear whether the disease can be prevented. Herein, we assessed whether a paternal fish oil diet could attenuate the development of new BPD in the offspring of toxicant exposed mice, with and without neonatal formula feeding. We investigated the impact of a paternal fish oil diet preconception because we previously reported that this intervention reduces the risk of TCDD associated placental dysfunction, prematurity, and low birth weight. We found that a paternal fish oil diet significantly reduced the risk of new BPD in neonatal mice with a history of paternal toxicant exposure regardless of neonatal diet. Furthermore, our evidence suggests that the protective effects of a paternal fish oil diet are mediated in part by the modulation of small molecules involved in EMT. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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18 pages, 2631 KiB

Open AccessFeature PaperArticle

The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice

by Conner L. Kennedy, Audrey Spiegelhoff, Kathy Wang, Thomas Lavery, Alexandra Nunez, Robbie Manuel, Lauren Hillers-Ziemer, Lisa M. Arendt and Kimberly P. Keil Stietz

Toxics 2021, 9(9), 214; https://doi.org/10.3390/toxics9090214 - 08 Sep 2021

Cited by 3 | Viewed by 2270

Abstract

Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls [...] Read more.

Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls (PCBs) leads to changes in immune cells within the bladder of young mice. Female mice were exposed to an environmentally relevant mixture of PCBs through gestation and lactation, and bladders were collected from offspring at postnatal day (P) 28–31. We identify several dose- and sex-dependent PCB effects in the bladder. The lowest concentration of PCB (0.1 mg/kg/d) increased CD45+ hematolymphoid immune cells in both sexes. While PCBs had no effect on CD79b+ B cells or CD3+ T cells, PCBs (0.1 mg/kg/d) did increase F4/80+ macrophages particularly in female bladder. Collagen density was also examined to determine whether inflammatory events coincide with changes in the stromal extracellular matrix. PCBs (0.1 mg/kg/d) decreased collagen density in female bladder compared to control. PCBs also increased the number of cells undergoing cell division predominantly in male bladder. These results implicate perturbations to the immune system in relation to PCB effects on the bladder. Future study to define the underlying mechanisms could help understand how environmental factors can be risk factors for lower urinary tract symptoms. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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10 pages, 888 KiB

Open AccessCommunication

Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice

by Karl F. W. Foley, Daniel Barnett, Deborah A. Cory-Slechta and Houhui Xia

Toxics 2021, 9(9), 206; https://doi.org/10.3390/toxics9090206 - 31 Aug 2021

Cited by 3 | Viewed by 1838

Abstract

Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to [...] Read more.

Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to shed light on potential mechanistic underpinnings, including changes in synaptic transmission and plasticity. However, previous studies relied on extended exposure into adulthood, and little is known about the effect of arsenic exposure in early development. Here, we studied the effects of early developmental arsenic exposure in juvenile mice on synaptic transmission and plasticity in the hippocampus. C57BL/6J females were exposed to arsenic (0, 50 ppb, 36 ppm) via drinking water two weeks prior to mating, with continued exposure throughout gestation and parturition. Electrophysiological recordings were then performed on juvenile offspring prior to weaning. In this paradigm, the offspring are exposed to arsenic indirectly, via the mother. We found that high (36 ppm) and relatively low (50 ppb) arsenic exposure both decreased basal synaptic transmission. A compensatory increase in pre-synaptic vesicular release was only observed in the high-exposure group. These results suggest that indirect, ecologically relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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Review

Jump to: Research

24 pages, 773 KiB

Open AccessReview

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

by Nelson T. Peterson and Chad M. Vezina

Toxics 2022, 10(2), 89; https://doi.org/10.3390/toxics10020089 - 16 Feb 2022

Cited by 2 | Viewed by 5649

Abstract

Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little [...] Read more.

Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little research has been dedicated to the influence of environmental chemicals on disease initiation, progression, or severity. Despite a few recent studies indicating a potential developmental origin of male LUTD linked to chemical exposures in the womb, it remains a grossly understudied endpoint in toxicology research. Therefore, we direct this review to toxicologists who are considering male LUTD as a new aspect of chemical toxicity studies. We focus on the LUTD disease process in men, as well as in the male mouse as a leading research model. To introduce the disease process, we describe the physiology of the male lower urinary tract and the cellular composition of lower urinary tract tissues. We discuss known and suspected mechanisms of male LUTD and examples of environmental chemicals acting through these mechanisms to contribute to LUTD. We also describe mouse models of LUTD and endpoints to diagnose, characterize, and quantify LUTD in men and mice. Full article

(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)

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