Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Association of pulmonary black carbon accumulation with cardiac fibrosis in residents of Sao Paulo, Brazil.

Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post-mortem samples. This study examined whether long-term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbon-based particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long-term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.

Effect of chronic exposure to fine particulate matter on cardiac tissue of NZBWF1 mice.

Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM) is associated with development of cardiovascular diseases. Long-term exposure to PM may increase the risk of cardiovascular events and reduce life expectancy. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, autoimmune in nature, that is characterized by the production of autoantibodies that affects several organs, including the heart. Air pollution - which can be caused by several different factors - may be one of the most important points both at the onset and the natural history of SLE. Therefore this study aims to investigate whether exposure to air pollution promotes increased inflammation and cardiac remodelling in animals predisposed to SLE. Female NZBWF1 mice were exposed to an environmental particle concentrator. Aspects related to cardiac remodelling, inflammation and apoptosis were analysed in the myocardium. Body weight gain, cardiac trophism by heart/body weight ratio, relative area of cardiomyocytes and the fibrotic area of cardiac tissue were evaluated during the exposure period. Animals exposed to PM2.5 showed increased area of cardiomyocytes, and area of fibrosis; in addition, we observed an increase in IL-1 and C3 in the cardiac tissue, demonstrating increased inflammation. We suggest that air pollution is capable of promoting cardiac remodelling and increased inflammation in animals predisposed to SLE.

Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.

The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM2.5) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM2.5 exposed only. Both, early life allergic sensitization and PM2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth.

LPS Response Is Impaired by Urban Fine Particulate Matter.

Fine particulate matter (PM2.5) is a complex mixture of components with diverse chemical and physical characteristics associated with increased respiratory and cardiovascular diseases mortality. Our study aimed to investigate the effects of exposure to concentrated PM2.5 on LPS-induced lung injury onset. BALB/c male mice were exposed to either filtered air or ambient fine PM2.5 in an ambient particle concentrator for 5 weeks. Then, an acute lung injury was induced with nebulized LPS. The animals were euthanized 24 h after the nebulization to either LPS or saline. Inflammatory cells and cytokines (IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-17, TNF) were assessed in the blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, lung morphology was assessed by stereological methods. Our results showed that the PM+LPS group showed histological evidence of injury, leukocytosis with increased neutrophils and macrophages, and a mixed inflammatory response profile, with increased KC, IL-6, IL-1ß, IL-4, and IL-17. Our analysis shows that there is an interaction between the LPS nebulization and PM2.5 exposure, differently modulating the inflammatory response, with a distinct response pattern as compared to LPS or PM2.5 exposure alone. Further studies are required to explain the mechanism of immune modulation caused by PM2.5 exposure.

Chronic exposure to PM2.5 aggravates SLE manifestations in lupus-prone mice.

BACKGROUND: Air pollution causes negative impacts on health. Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations and multifactorial etiology. Recent studies suggest that air pollution can trigger SLE and induce disease activity. However, this association has not been deeply investigated. Thus, the aim of this study was to evaluate whether exposure to fine particulate matter (PM2.5) exacerbates SLE manifestations, focusing on renal complications, in a lupus-prone animal model. Female NZBWF1 mice were exposed daily to 600 µg/m3 of inhaled concentrated ambient particles (CAP) or filtered air (FA). Survival rate, body weight, weight of organs (kidney, spleen, thymus, liver and heart), blood cell count, proteinuria, kidney stereology, renal histopathology, gene expression and oxidative stress were analyzed. RESULTS: Female NZBW mice exposed to CAP showed decreased survival, increased circulating neutrophils, early onset of proteinuria and increased kidney weight with renal cortex enlargement when compared to NZBW mice exposed to FA. CONCLUSIONS: This work shows that air pollution aggravates some SLE manifestations in lupus-prone mice. These results reinforce the need of reducing air pollutant levels in order to promote a better quality of life for individuals diagnosed with SLE.

Immune-pineal axis protects rat lungs exposed to polluted air.

Environmental pollution in the form of particulate matter <2.5 µm (PM2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.

Effects of cannabis and its components on the retina: a systematic review.

Purpose: Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.Methods: We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed.Results: We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.Conclusions: This review suggests that cannabinoids may have an important role in retinal processing and function.

Pleural anthracosis as an indicator of lifetime exposure to urban air pollution: An autopsy-based study in Sao Paulo.

Many studies have been conducted to evaluate the association between air pollution and adverse health effects using a wide variety of methods to assess exposure. However, the assessment of individual long-term exposure to ambient air pollution is a challenging task and has not been evaluated in a large autopsy study. Our goal was to investigate whether exposure to urban air pollution is associated to the degree of lung anthracosis, considering modifying factors such as personal habits, mobility patterns and occupational activities. We conducted a study in Sao Paulo, Brazil from February 2017 to June 2018, combining epidemiological, spatial analysis and autopsy-based approaches. Information about residential address, socio-demographic details, occupation, smoking status, time of residence in the city and time spent commuting was collected via questionnaires applied to the next-of-kin. Images of the pleura surface from upper and lower lobes were used to quantify anthracosis in the lungs. We used multiple regression models to assess the association between the amount of carbon deposits in human lungs, measured by the fraction of pleural anthracosis (FA), and potential explanatory variables. We analyzed 413 cases and our data showed that for each additional hour spent in daily commuting, the ratio FA/(1-FA) is multiplied by 1.05 (95% confidence interval: [1.02; 1.08]). The estimated coefficient for daily hours spent in traffic was not considerably affected by the inclusion of socio-demographic variables and smoking habits. We estimate a tobacco equivalent dose of 5 cigarettes per day in a city where annual PM2.5 concentration oscillates around 25 µg/m3. Pleural anthracosis is a potential index of lifetime exposure to traffic-derived air pollution.

Diesel exhaust exposure intensifies inflammatory and structural changes associated with lung aging in mice.

Life expectancy is increasing worldwide. Lung aging is a process marked by changes in multiple morphological, physiological and age-related biomarkers (e.g., sirtuins) and is influenced by external factors, such as air pollution. Hence, the elderly are considered more vulnerable to the air pollution hazards. We hypothesized that diesel exhaust (DE) exposure intensifies changes in lung inflammatory and structural parameters in aging subjects. Two- and fifteen-month-old mice were exposed to DE for 30 days. Lung function was measured using the forced oscillation method. The inflammatory profile was evaluated in the bronchoalveolar lavage fluid (BALF) and blood, and lung volumes were estimated by stereology. Antioxidant enzyme activity was evaluated by spectrophotometry, sirtuin 1 (SIRT1), sirtuin 2 (SIRT2) and sirtuin 6 (SIRT6) expression was assessed by reverse transcription polymerase chain reaction (RT-PCR), and levels of the sirtuin proteins were evaluated by immunohistochemical staining in lung tissues. Older mice presented decreased pulmonary resistance and elastance, increased macrophage infiltration and decreased tumor necrosis factor (TNF) and interleukin 10 (IL-10) levels in the BALF, reduced activities of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), and increased activity glutathione S-transferase (GST); increased lung volumes with decreased elastic fiber and increased airway collagen content. SIRT1 gene expression was decreased in older animals, but protein levels were increased. DE exposure increased macrophage infiltration and oxidative stress in the lungs of animals of both ages. SIRT6 gene expression was decreased by DE exposure, with increased protein levels. In older animals, DE affected lung structure and collagen content. Lung aging features, such as decreased antioxidant reserves, lower IL-10 expression, and decreased SIRT1 levels may predispose subjects to exacerbated responses after DE exposure. Our data support the hypothesis that strategies designed to reduce ambient air pollution are an important step towards healthy aging.

Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from São Paulo city, Brazil.

BACKGROUND: The Metropolitan Area of São Paulo has a unique composition of atmospheric pollutants, and positive correlations between exposure and the risk of diseases and mortality have been observed. Here we assessed the effects of ambient fine particulate matter (PM2.5) on genotoxic and global DNA methylation and hydroxymethylation changes, as well as the activities of antioxidant enzymes, in tissues of AJ mice exposed whole body to ambient air enriched in PM2.5, which was concentrated in a chamber near an avenue of intense traffic in São Paulo City, Brazil. RESULTS: Mice exposed to concentrated ambient PM2.5 (1 h daily, 3 months) were compared to in situ ambient air exposed mice as the study control. The concentrated PM2.5 exposed group presented increased levels of the oxidized nucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine in lung and kidney DNA and increased levels of the etheno adducts 1,N6-etheno-2'-deoxyadenosine and 1,N2-etheno-2'-deoxyguanosine in kidney and liver DNA, respectively. Apart from the genotoxic effects, the exposure to PM2.5 led to decreased levels of the epigenetic mark 5-hydroxymethylcytosine (5-hmC) in lung and liver DNA. Changes in lung, liver, and erythrocyte antioxidant enzyme activities were also observed. Decreased glutathione reductase and increased superoxide dismutase (SOD) activities were observed in the lungs, while the liver presented increased glutathione S-transferase and decreased SOD activities. An increase in SOD activity was also observed in erythrocytes. These changes are consistent with the induction of local and systemic oxidative stress. CONCLUSIONS: Mice exposed daily to PM2.5 at a concentration that mimics 24-h exposure to the mean concentration found in ambient air presented, after 3 months, increased levels of DNA lesions related to the occurrence of oxidative stress in the lungs, liver, and kidney, in parallel to decreased global levels of 5-hmC in lung and liver DNA. Genetic and epigenetic alterations induced by pollutants may affect the genes committed to cell cycle control, apoptosis, and cell differentiation, increasing the chance of cancer development, which merits further investigation.

Before the first breath: prenatal exposures to air pollution and lung development.

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats.

AIMS: Investigate the effect of a novel cell-based therapy with skeletal muscle-derived mononuclear cells (SMDMCs) in a rat model of stress urinary incontinence. METHODS: Male Wistar-Kyoto rats' hind limb muscles were enzymatically dissociated, and SMDMCs were isolated without needing expansion. The cell population was characterized. Twenty female rats underwent urethrolysis. One week later, 10 rats received periurethral injection of 106 cells (SMDMC group), and 10 rats received saline injections (Saline group). Ten rats underwent sham surgery (Sham group). Four weeks after injection, animals were euthanized and the urethra was removed. The incorporation of SMDMCs in the female urethra was evaluated with fluorescence in situ hybridization for the detection of Y-chromosomes. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemistry for actin and myosin were performed. The muscle/connective tissue, actin and myosin ratios were calculated. Morphological evaluation of the urethral diameters and fractional areas of the lumen, mucosa, and muscular layer was performed. RESULTS: SMDMCs population was consistent with the presence of muscle cells, muscle satellite cells, perivascular cells, muscle progenitor cells, and endothelial cells. SMDMCs were incorporated into the urethra. A significant decrease in the muscle/connective tissue ratio was observed in the Saline group compared with the SMDMC and Sham groups. The proportions of actin and myosin were significantly decreased in the Saline group. No differences were observed in the morphometric parameters. CONCLUSIONS: SDMSC were incorporated into the rat urethra and promoted histological recovery of the damaged urethral sphincter, resulting in decreased connective tissue deposition and increased muscle content.

Ambient levels of concentrated PM2.5 affects cell kinetics in adrenal glands: an experimental study in mice.

We evaluated the effects of air pollution on the adrenal cortex using 30 female mice divided into two groups of fifteen animals each. One group was conditioned daily in a chamber with exposure to particulate matter (PM) 2.5 µm (GExp). Animals were exposed on daily basis in an ambient particles concentrator during the period of time enough to reach an accumulated dose of 600 µg/m3, which corresponds to a 24-h exposure of 25 µg/m3 that approximates to the annual mean of PM2.5 in São Paulo. The other group was allocated to another chamber with filtered air (GCrt). After euthanasia, the adrenals underwent histological processing and immunohistochemistry staining for Ki-67 and cleaved caspase-3. Histomorphometry of the adrenal glands in GExp showed increased thickness of the zona glomerulosa, while in GCrt; the adrenal glands from GExp had higher Ki-67 immunostaining scores in the zona reticularis than those from GCrt. The adrenal from GExp showed higher cleaved caspase-3 immunoreactivity in the zona fasciculata than the unexposed group (GCrt). The homeostasis index indicated higher cell proliferation in the zona glomerulosa and zona reticularis in GExp than in GCrt. Our data indicate that PM2.5 air pollution induces alterations on cell kinetics in mouse adrenal glands.

Tenofovir during pregnancy in rats: a novel pathway for programmed hypertension in the offspring.

OBJECTIVES: To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy. METHODS: Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed. RESULTS: Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion. CONCLUSIONS: This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.

Air pollution accelerates the development of obesity and Alzheimer's disease: the role of leptin and inflammation - a mini-review.

Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM2.5) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD). PM2.5 contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low-and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM2.5 exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.

Exposure to urban ambient particles (PM2.5) before pregnancy affects the expression of endometrial receptive markers to embryo implantation in mice: Preliminary results.

Air pollution (AP) is one of the main recent concerns in reproductive healthy due to its potential to promote negative outcomes during pregnancy and male and female fertility. Several studies have demonstrated that AP exposure has been linked to increased embryonic implantation failures, alterations in embryonic, fetal and placental development. For a well-succeeded implantation, both competent blastocyst and receptive endometrium are required. Based on the lack of data about the effect of AP in endometrial receptivity, this study aimed to evaluate he particulate matter (PM) exposure impact on uterine receptive markers in mice and associate the alterations to increased implantation failures due to AP. For this study, ten dams per group were exposed for 39 days to either filter (F) or polluted air (CAP). At fourth gestational day (GD4), females were euthanized. Morphological, ultrastructural, immunohistochemical and molecular analysis of uterine and ovarian samples were performed. CAP-exposed females presented a reduced number of corpus luteum; glands and epithelial cells were increased with pinopodes formation impairment. Immunohistochemistry analysis revealed decreased LIF protein levels. These preliminary data suggests that PM exposure may exert negative effects on endometrial receptivity by affecting crucial parameters to embryonic implantation as uterine morphological differentiation, corpus luteum quantity and LIF expression during implantation window.

Epoxiconazole-induced degeneration in rat placenta and the effects of estradiol supplementation.

Epoxiconazole (CAS-No. 133855-98-8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7-18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole-mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose-dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 µg of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter.

Comparative stereological evaluation of the term allantochorion membrane in the mare pregnant with mule foals and equine foals.

Mules are derived from crossing horse mares with a donkey, in which the interest is due to gentleness and ability to work and equestrian sports. As the placenta is responsible for fetal development and maturation, knowing its typical microstructure allows us to understand how fetomaternal interactions occur in this interspecific pregnancy. Thus, the study performed a comparative stereological evaluation of volumetric composition and fetomaternal contact surface in the uterine body (UB), gravid uterine horn (GUH), and nongravid uterine horn (NGUH) of Mangalarga Paulista mare's term allantochorion membrane in mule and equine pregnancies. In equine gestation, the UB microcotyledon surface density was negatively correlated with the NGUH absolute area and the total volume of microvilli. In mule gestation, the base width and the number of microcotyledon were negatively correlated with the height and number of microcotyledons in the NGUH. Mule also showed a negative correlation between (1) the UB microcotyledon surface density and the GUH microcotyledons number per unit of membrane length, (2) the GUH total volume and the NGUH microcotyledon number. Such differences demonstrate a compensatory mechanism in conversion capacity among macrocompartments. A trend toward a greater total volume of allantoid vessels and total volume of allantoid mesoderm in UB microvilli was found in the equine and mule groups, respectively. There was a significant increase in the base width of microcotyledons in the NGUH of mules versus horses. These finds possibly influence the exchange capacity of each placental microregion and suggest a difference between mule versus horse term allantochorion membrane.

A custom, low-cost, continuous flow chamber built for experimental Sargassum seaweed decomposition and exposure of small rodents to generated gaseous products.

Since 2011, Sargassum events have increased in frequency along the Caribbean and Atlantic coasts. The accumulation and decomposition of large amounts of Sargassum seaweed on beaches pose socio-economic, ecological, and health risks due to the emission of hydrogen sulfide (H2S), methane, and ammonia. However, limited research exists on the emission processes and the health effects of subchronic and chronic exposure to low levels of H2S. Additionally, the absence of emission factor data for Sargassum decomposition on-site makes health risk assessments challenging. This study aimed to create a custom chamber to simulate real-world Sargassum decomposition, exposing experimental animals to the generated gases. Metal content was analyzed, and emission rates were estimated in a controlled environment. The decomposition-exposure system replicated reported environmental gas emissions from the Caribbean region, except for NH3. H2S bursts were observed during the decomposition process at intervals of 2-10 days, with higher frequency associated with larger masses of decomposing Sargassum. The decomposed gas was transferred to the exposure chamber, resulting in an 80-87% reduction in H2S concentration. The maximum H2S emission was 156 ppm, with a concentration ranging from 50.4 to 56.5 ppm. An estimated emission rate of 7-8 g/h for H2S was observed, and significant levels of lead, arsenic, and aluminum were found in beached Sargassum from the northeast coast of Brazil. This study's developed model provides an opportunity to investigate the effects and risks to human health associated with exposure to gases produced during the environmental decomposition of Sargassum seaweed.