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Tris(4-hydroxyphenyl)ethane (THPE), a trisphenol compound, is antiestrogenic and can retard uterine development in CD-1 mice
2020
Xiao, Han | Wang, Yue | Jia, Xiaojing | Yang, Lei | Wang, Xiaoning | Guo, Xuan | Zhang, Zhaobin
Tris (4-hydroxyphenyl)ethane (THPE), a trisphenol compound widely used as a branching agent and raw material in plastics, adhesives, and coatings is rarely regarded with concern. However, inspection of in vitro data suggests that THPE is an antagonist of estrogen receptors (ERs). Accordingly, we aimed to evaluate the antiestrogenicity of THPE in vivo and tested its effect via oral gavage on pubertal development in female CD-1 mice. Using uterotrophic assays, we found that THPE either singly, or combined with 17β-estradiol (E₂) (400 μg/kg bw/day) suppressed the uterine weights at low doses (0.1, 0.3, and 1 mg/kg bw/day) in 3-day treatment of weaning mice. When mice were treated with THPE during adolescence (for 10 days beginning on postnatal day 24), their uterine development was significantly retarded at doses of at least 0.1 mg/kg bw/day, manifest as decreased uterine weight, atrophic endometrial stromal cells and thinner columnar epithelial cells. Transcriptome analyses of uteri demonstrated that estrogen-responsive genes were significantly downregulated by THPE. Molecular docking shows that THPE fits well into the antagonist pocket of human ERα. These results indicate that THPE possesses strong antiestrogenicity in vivo and can disrupt normal female development in mice at very low dosages.
Показать больше [+] Меньше [-]Perfluoroalkyl acids in paired serum, urine, and hair samples: Correlations with demographic factors and dietary habits
2019
Kim, Da-Hye | Lee, Jong Hyeon | Oh, Jeong-Eun
We analyzed paired serum, urine, and hair samples from 94 Korean children and adults to investigate levels of 11 perfluoroalkyl acids (PFAAs). The effects of demographic factors and dietary habits on PFAA exposure were also assessed based on the paired samples. The total PFAA concentrations were 2.4–31 ng/mL in serum, not detected–9.5 ng/mL in urine, and 0.48–15 ng/g in hair. Levels of perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), which have short carbon chains, were 1.5–5 fold higher in urine and hair than in serum. The PFAA concentrations in serum exhibited a decreasing trend with age from young childhood to adolescence, followed by an increasing trend after adolescence. For most PFAA species, concentrations in serum were higher in adult males than in adult females (p < 0.01). No sex difference was evident in the urine and hair samples. In addition, there was no age difference in the urine samples, but in the hair samples, we observed higher concentrations of PFAAs in children than in the other age groups (p < 0.01). The consumption rates of fish and water showed significant correlations with serum (positive correlation) and hair (negative) concentrations, respectively. No relationships between serum and hair/urine levels for most PFAAs were observed, except between serum and hair levels for perfluorooctanoic acid (PFOA).
Показать больше [+] Меньше [-]Health effects in people relocating between environments of differing ambient air pollution concentrations: A literature review
2022
Edwards, Leslie | Wilkinson, Paul | Rutter, Gemma | Milojevic, Ai
People who relocate to a new environment may experience health effects from a change in ambient air pollution. We undertook a literature review of studies of such relocations and health effects and report the results as a narrative analysis. Fifteen articles of heterogeneous designs met the inclusion criteria. Four short-term (relocation duration less than six months) and three long-term (relocation duration six months or greater) studies reported evidence of the effect of relocation on physiological outcome, biomarkers or symptoms. All had potential weaknesses of design or analysis but, as a whole, their results are broadly consistent in suggesting short-term adverse effects of air pollutants or their reversibility. One long-term study provided evidence that changes in air pollution exposure during adolescence have a measurable effect on lung function growth. Four cohort studies were also identified that used relocation to strengthen evidence of air-pollution-exposure relationships by using a design that incorporates effective randomization of exposure or the use of relocation to improve exposure classification. However, three studies of relocation during pregnancy provided limited evidence to conclude an effect of relocation-related change in exposure on pregnancy outcome. Overall, most relocation studies are consistent with short- or long-term adverse effects of air pollution on biological function or mortality, but many studies of change in exposure have design weaknesses that limit the robustness of interpretation. We outline principles for improved design and analysis to help strengthen future studies for the insights they can provide from their quasi-experimental designs, including on the nature and timing of functional changes of relocation-related changes in exposure to ambient air pollution.
Показать больше [+] Меньше [-]Environmental exposure to 17β-trenbolone during adolescence inhibits social interaction in male mice
2021
Zhang, Shaozhi | Jiao, Zihao | Zhao, Xin | Sun, Mingzhu | Feng, Xizeng
Puberty is a critical period for growth and development. This period is sensitive to external stimuli, which ultimately affects the development of nerves and the formation of social behaviour. 17β-Trenbolone (17β-TBOH) is an endocrine disrupting chemicals (EDCs), which had been widely reported in aquatic vertebrates. But there is little known about the effects of 17β-TBOH on mammals, especially on adolescent neurodevelopment. In this study, we found that 17β-TBOH acute 1 h exposure can cause the activation of the dopamine circuit in pubertal male balb/c mice. At present, there is little known about the effects of puberty exposure of endocrine disruptors on these neurons/nerve pathways. Through a series of behavioural tests, exposure to 80 μgkg⁻¹ d⁻¹ of 17β-TBOH during adolescence increased the anxiety-like behaviour of mice and reduced the control of wheel-running behaviour and the response of social interaction behaviour. The results of TH immunofluorescence staining showed that exposure to 17β-TBOH reduced dopamine axon growth in the medial prefrontal cortex (mPFC). In addition, the results of real-time PCR showed that exposure to 17β-TBOH not only down-regulated the expression of dopamine axon development genes, but also affected the balance of excitatory/inhibitory signals in mPFC. In this research, we reveal the effects of 17β-TBOH exposure during adolescence on mammalian behaviour and neurodevelopment, and provide a reference for studying the origin of adolescent diseases.
Показать больше [+] Меньше [-]Early life exposure to greenness and executive function and behavior: An application of inverse probability weighting of marginal structural models
2021
Jimenez, Marcia P. | Aris, Izzuddin M. | Rifas-Shiman, Sheryl | Young, Jessica | Tiemeier, Henning | Hivert, Marie-France | Oken, Emily | James, Peter
Increasingly, studies suggest benefits of natural environments or greenness on children's health. However, little is known about cumulative exposure or windows of susceptibility to greenness exposure. Using inverse probability weighting of marginal structural models (IPW/MSM), we estimated effects of greenness exposure from birth through adolescence on executive function and behavior. We analyzed data of 908 children from Project Viva enrolled at birth in 1999–2002 and followed up until early adolescence. In mid-childhood (median 7.7 years) and early adolescence (13.1 years), executive function and behavior were assessed using the Behavior Rating Inventory of Executive Function and the Strengths and Difficulties Questionnaire (SDQ). Greenness was measured at birth, early childhood, mid-childhood, and early adolescence, using the Normalized Difference Vegetation Index. We used inverse probability weighting of marginal structural models to estimate effects of interventions that ensure maximum greenness exposure versus minimum through all intervals; and that ensure maximum greenness only in early childhood (vs. minimum through all intervals). Results of the effects of “maximum (vs. minimum) greenness at all timepoints” did not suggest associations with mid-childhood outcomes. Estimates of “maximum greenness only in early childhood (vs. minimum)” suggested a beneficial association with mid-childhood SDQ (−3.21, 99 %CI: −6.71,0.29 mother-rated; −4.02, 99 %CI: −7.87,-0.17 teacher-rated). No associations were observed with early adolescent outcomes. Our results for “persistent” maximum greenness exposure on behavior, were not conclusive with confidence intervals containing the null. The results for maximum greenness “only in early childhood” may shed light on sensitive periods of greenness exposure for behavior regulation.
Показать больше [+] Меньше [-]B-vitamin supplementation ameliorates anxiety- and depression-like behavior induced by gestational urban PM2.5 exposure through suppressing neuroinflammation in mice offspring
2020
Wang, Xia | Wang, Tingting | Sun, Lijuan | Zhang, Haoyun | Liu, Chong | Zhang, Can | Yu, Li
PM₂.₅ exposure is an emerging environmental concern and severe health insult closely related to psychological conditions such as anxiety and depression in adolescence. Adolescence is a critical period for neural system development characterized by continuous brain maturation, especially in the prefrontal cortex. The etiology of these adolescent conditions may derive from fetal origin, probably attributed to the adverse effects induced by intrauterine environmental exposure. Anxiety- and depression-like behavior can be induced by gestational exposure to PM₂.₅ in mice offspring which act as a useful model system. Recent studies show that B-vitamin may alleviate PM₂.₅-induced hippocampal neuroinflammation- and function-related spatial memory impairment in adolescent mice offspring. However, cortical damage and related neurobehavioral defects induced by gestational PM₂.₅ exposure, as well as the potential reversibility by interventions in mice offspring require to be elucidated. Here, we aimed to investigate whether B-vitamin would protect mice offspring from the adverse effects derived from gestational exposure to urban PM₂.₅ on cortical areas to which anxiety and depression are closely related. Pregnant mice were divided into three groups: control group (treated with PBS alone), model group (treated with both PM₂.₅ and PBS), and intervention group (treated with both PM₂.₅ and B-vitamin), respectively. The mice offspring were then applied to comprehensive neurobehavioral, ultrastructural, biochemical, and molecular biological analyses. Interestingly, we observed that gestational PM₂.₅ exposure led to neurobehavioral defects including anxiety- and depression-like behavior. In addition, neuroinflammation, oxidative damage, increased apoptosis, and caspase-1-mediated inflammasome activation in the prefrontal cortex were observed. Notably, both behavioral and molecular changes could be significantly alleviated by B-vitamin treatment. In summary, our results suggest that the anxiety- and depression-like behavior induced by gestational PM₂.₅ exposure in mice offspring can be ameliorated by B-vitamin supplementation, probably through the suppression of apoptosis, oxidative damage, neuroinflammation, and caspase-1-mediated inflammasome activation.
Показать больше [+] Меньше [-]PM2.5 exposure in utero contributes to neonatal cardiac dysfunction in mice
2017
Tanwar, Vineeta | Adelstein, Jeremy M. | Grimmer, Jacob A. | Youtz, Dane J. | Sugar, Benjamin P. | Wold, Loren E.
Exposure of fine particulate matter (PM2.5) to pregnant dams has been shown to be strongly associated with adverse cardiovascular outcomes in offspring at adulthood, however, effects evident during neonatal periods are unclear. We designed this study to examine cardiac function of neonatal mice (14 days old) exposed to in utero PM2.5.Pregnant FVB female mice were exposed either to filtered air (FA) or PM2.5 at an average concentration of 91.78 μg/m3 for 6 h/day, 5 days/wk (similar to exposure in a large industrial area) throughout the gestation period (21 days). After birth, animals were analyzed at day 14 of life.Fourteen day old mice exposed to PM2.5 during the in utero period demonstrated decreased fractional shortening (%FS, 41.1 ± 1.2% FA, 33.7 ± 1.2% PM2.5, p < 0.01) and LVEDd (2.87 ± 0.08 mm FA, 2.58 ± 0.07 mm PM2.5, p < 0.05) compared to FA exposed mice. Contractile kinetics and calcium transients in isolated cardiomyocytes from PM2.5 exposed mice illustrated reduced peak shortening (%PS, 16.7 ± 0.5% FA, 14.7 ± 0.4% PM2.5, p < 0.01), negative contractile velocity (-dL/dT, −6.91 ± 0.3 μm/s FA, −5.46 ± 0.2 μm/s PM2.5, p < 0.001), increased time to relaxation 90% (TR90, 0.07 ± 0.003 s FA, 0.08 ± 0.004 s PM2.5, p < 0.05), decreased calcium transient amplitude (Δ340/380, 33.8 ± 3.4 FA, 29.5 ± 2.8 p.m.2.5) and slower fluorescence decay rate (τ, 0.72 ± 0.1 s FA, 1.16 ± 0.15 s PM2.5, p < 0.05). Immunoblotting studies demonstrated alterations in expression of Ca2+ handling proteins- SERCA-2A, p-PLN, NCX and CaV1.2 in hearts of 14 day old in utero PM2.5 exposed mice compared to FA exposed hearts.PM2.5 exposure during the critical in utero period adversely affects the developing mouse fetus leading to functional cardiac changes that were evident during the very early (14 days) stages of adolescence. These data demonstrated that exposure to PM2.5 during the gestation period significantly impacts cardiovascular outcomes early in life.
Показать больше [+] Меньше [-]Overview of Traditional and Environmental Factors Related to Bone Health
2022
Rubio-Gutierrez, Juan Carlos | Mendez-Hernández, Pablo | Guéguen, Yann | Galichon, Pierre | Tamayo-Ortiz, Marcela | Haupt, Karsten | Medeiros, Mara | Barbier, Olivier Christophe
Bone mass in adulthood depends on growth and mineralization acquired during childhood and adolescence. It is well known that these stages of life are crucial for bone development, where genetic, nutritional, hormonal, and lifestyle factors play a significant role. Bone loss is normally a natural and slow process that begins years later after the peak bone mass is achieved and continues throughout the lifespan. Lifestyle choices in childhood and adolescence such as minimal physical activity, excessive caffeine or carbonated beverages intake, malnutrition, cigarette use, or high alcohol consumption and other factors like environmental pollutants can also negatively affect bone health and accelerate the bone loss process. The aim of this work is an overview of risk factors associated with inadequate bone health in early life.
Показать больше [+] Меньше [-]Prenatal di-(2-ethylhexyl) phthalate maternal exposure impairs the spatial memory of adult mouse offspring in a phase- and gender-dependent manner
2020
Zhao, Ling-Li | Shen, Ru | Sun, Cong-Cong | Zhang, Shan-Yu | Wang, Bo | Sun, Mei-Fang | Xu, De-Xiang
DEHP is a wildly used plasticizer. Maternal DEHP exposure induced fetal growth restriction (FGR) and behavioral abnormalities in adolescence and adulthood mouse. The effect of low birth weight induced by DEHP on behaviors after growing up is not certain. In this study, the ICR pregnant mice were exposed to 200 mg/kg DEHP during gestation 6–12 days or 13–17 days, which can create FGR model. The F1 offspring were performed three ethological experiments at puberty (6 weeks postpartum) and adult period (8 weeks postpartum). The open field test was performed to detect the locomotor activity and anxiety, the elevated plus maze to test anxiety-like behavior, and the Morris water maze assay to measure the spatial learning and memory capability of male and female offspring. The results showed that spatial memory ability was dramatically impaired for male rather than female offspring in gestation 13–17 days’ group. Other behaviors had no statistically different between groups. These findings suggest that prenatal DEHP exposure disturbed mouse offspring spatial memory ability in a phase- and gender-dependent manner.
Показать больше [+] Меньше [-]Meta-analysis and experimental validation identified atrazine as a toxicant in the male reproductive system
2021
Zhu, Shenhao | Zhang, Tongtong | Wang, Yuhao | Zhou, Xiang | Wang, Shangqian | Wang, Zengjun
Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA’s guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = − 0.90, 95% CI − 1.27 to − 0.53), and reduced absolute weights of testis (SMD = − 0.41, 95% CI − 0.61 to − 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = − 2.32, 95% CI − 2.83 to − 1.81) and testis (SMD = − 1.01, 95% CI − 1.37 to − 0.64), decrease in sperm motility (SMD = − 8.86, 95% CI − 10.88 to − 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.
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