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Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd-exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd-exposed rats had increased liver cholesterol levels, insulin receptor beta (IRß) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.
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Cadmio , Diabetes Mellitus Tipo 2 , Hígado , Animales , Femenino , Diabetes Mellitus Tipo 2/inducido químicamente , Ratas , Cadmio/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Tipo 1/inducido químicamente , Ratas Wistar , Páncreas/efectos de los fármacos , Páncreas/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Disruptores Endocrinos/toxicidadRESUMEN
This study's objective was to understand Colombian adolescents' experiences and preferences regarding access to sexual and reproductive health services (SRHS), either alone or accompanied. A mixed-method approach was used, involving a survey of 812 participants aged eleven to twenty-four years old and forty-five semi-structured interviews with participants aged fourteen to twenty-three. Previous research shows that adolescents prefer privacy when accessing SRHS and often do not want their parents involved. Such findings align with the longstanding tendency to frame the ethical principle of autonomy as based on independence in decision-making. However, the present study shows that such a conceptualization and application of autonomy does not adequately explain Colombian adolescent participants' preferences regarding access to SRHS. Participants shared a variety of preferences to access SRHS, with the majority of participants attaching great importance to having their parents involved, to varying degrees. What emerges is a more complex and non-homogenous conceptualization of autonomy that is not inherently grounded in independence from parental involvement in access to care. We thus argue that when developing policies involving adolescents, policymakers and health professionals should adopt a nuanced "relational autonomy" approach to better respect the myriad of preferences that Colombian (and other) adolescents may have regarding their access to SRHS.
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Accesibilidad a los Servicios de Salud , Autonomía Personal , Servicios de Salud Reproductiva , Humanos , Adolescente , Colombia , Servicios de Salud Reproductiva/ética , Accesibilidad a los Servicios de Salud/ética , Femenino , Masculino , Adulto Joven , Niño , Toma de Decisiones , Padres/psicología , Salud Sexual , Conducta Sexual , PrivacidadRESUMEN
Microcystin (MC) is most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis and metabolic function. In this study, we assessed whether MC exposure results in HPG axis and metabolic changes. Female rats were exposed to a single dose of MC at environmentally relevant levels (5, 20 and 40 µg/kg). After 24 h, we evaluated reproductive and metabolic parameters for 15 days. MC reduced the hypothalamic GnRH protein expression, increased the pituitary protein expression of GnRHr and IL-6. MC reduced LH levels and increased FSH levels. MC reduced the primary follicles, increased the corpora lutea, elevated levels of anti-Müllerian hormone (AMH) and progesterone, and decreased estrogen levels. MC increased ovarian VEGFr, LHr, AMH, ED1, IL-6 and Gp91-phox protein expression. MC increased uterine area and reduced endometrial gland number. A blunted estrogen-negative feedback was observed in MC rats after ovariectomy, with no changes in LH levels compared to intact MC rats. Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.
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Eje Hipotálamico-Pituitario-Gonadal , Microcistinas , Ratas , Femenino , Animales , Microcistinas/toxicidad , Interleucina-6/metabolismo , Ovario/metabolismo , Estrógenos , Hormona Liberadora de Gonadotropina/metabolismoRESUMEN
Introduction: Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative metabolism and myocardial contractility, we determined the effects of testosterone deficiency on the two spatially distinct subpopulations of cardiac mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM). Methods: We assessed cardiac function and cardiac mitochondria structure of SSM and IFM after 12 weeks of testosterone deficiency in male Wistar rats. Results and Discussion: Results show that low testosterone reduced myocardial contractility. Orchidectomy increased total left ventricular mitochondrial protein in the SSM, but not in IFM. The membrane potential, size and internal complexity in the IFM after orchidectomy were higher compared to the SHAM group. However, the rate of oxidative phosphorylation with all substrates in the IFM after orchidectomy was lower compared to the SHAM group. Testosterone replacement restored these changes. In the testosterone-deficient SSM group, oxidative phosphorylation was decreased with palmitoyl-L-carnitine as substrate; however, the mitochondrial calcium retention capacity in IFM was increased. There was no difference in swelling of the mitochondria in either group. These changes in IFM were followed by a reduction in phosphorylated form of AMP-activated protein kinase (p-AMPK-α), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) translocation to mitochondria and decreased mitochondrial transcription factor A (TFAM). Testosterone deficiency increased NADPH oxidase (NOX), angiotensin converting enzyme (ACE) protein expression and reduced mitochondrial antioxidant proteins such as manganese superoxide dismutase (Mn-SOD) and catalase in the IFM. Treatment with apocynin (1.5 mM in drinking water) normalized myocardial contractility and interfibrillar mitochondrial function in the testosterone depleted animals. In conclusion, our findings demonstrate that testosterone deficiency leads to reduced myocardial contractility and impaired cardiac interfibrillar mitochondrial function. Our data suggest the involvement of reactive oxygen species, with a possibility of NOX as an enzymatic source.
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Mitocondrias Cardíacas , Miocardio , Ratas , Animales , Masculino , Ratas Wistar , Miocardio/metabolismo , Estrés Oxidativo , Testosterona/farmacología , Testosterona/metabolismoRESUMEN
The ovaries play critical roles in regulating oocyte maturation and sex steroid hormone production and thus are critical for female reproduction. Ovarian function relies on hormone receptors and signaling pathways, making the ovaries potential targets for environmental factors, such as microcystins (MCs). MCs are a diverse group of cyanobacterial toxins generally found in eutrophic water or algal blooms. Here, we review relevant research on the associations between MC exposure and ovarian dysfunction, including their effects on ovarian morphology, folliculogenesis, steroid production, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, and fertility. This review covers the most recent in vitro and in vivo studies in mammals. We also discuss important gaps in the literature. Overall, current evidence indicates that MC exposure causes impairments in ovarian function, but further studies are needed to elucidate the mechanisms through which MCs affect ovarian function and other female endocrine functions.
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Microcistinas , Ovario , Animales , Femenino , Microcistinas/toxicidad , Toxinas Marinas , MamíferosRESUMEN
We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHß+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHß+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.
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Hipotálamo , Obesidad , Ratas , Femenino , Animales , Hipotálamo/metabolismo , Obesidad/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Dieta , Carbohidratos , Kisspeptinas/genética , Kisspeptinas/metabolismoRESUMEN
Phthalates are endocrine-disrupting chemicals used in consumer products. Although phthalates are obesogens and affect metabolic function, it is unknown if chronic exposure for 6 months to a phthalate mixture alters adipose tissue phenotype in female mice. After vehicle or mixture exposure, white adipose tissue and brown adipose tissue (WAT and BAT) were analyzed for expression of adipogenesis, proliferation, angiogenesis, apoptosis, oxidative stress, inflammation, and collagen deposition markers. The mixture altered WAT morphology, leading to an increase in hyperplasia, blood vessel number, and expression of BAT markers (Adipoq and Fgf2) in WAT. The mixture increased the expression of the inflammatory markers, Il1ß, Ccl2, and Ccl5, in WAT. The mixture also increased expression of the proapoptotic (Bax and Bcl2) and antiapoptotic (Bcl2l10) factors in WAT. The mixture increased expression of the antioxidant Gpx1 in WAT. The mixture changed BAT morphology by increasing adipocyte diameter, whitening area, and blood vessel number and decreased expression of the thermogenic markers Ucp1, Pgargc1a, and Adrb3. Furthermore, the mixture increased the expression of adipogenic markers Plin1 and Cebpa, increased mast cell number, and increased Il1ß expression in BAT. The mixture also increased expression of the antioxidant markers Gpx and Nrf2 and the apoptotic marker Casp2 in BAT. Collectively, these data indicate that chronic exposure to a phthalate mixture alters WAT and BAT lipid metabolism phenotypes in female mice, leading to an apparent shift in their normal morphology. Following long-term exposure to a phthalate mixture, WAT presented BAT-like features and BAT presented WAT-like features.
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Tejido Adiposo Pardo , Antioxidantes , Animales , Ratones , Femenino , Tejido Adiposo Pardo/metabolismo , Antioxidantes/metabolismo , Tejido Adiposo , Tejido Adiposo Blanco , Fenotipo , Ratones Endogámicos C57BL , Caspasa 2/metabolismoRESUMEN
Tributyltin (TBT) is an obesogenic endocrine disrupting chemical (EDC) linked with several metabolic complications. Brown adipose tissue (BAT) is the principal site for thermogenesis, making it a potential target for obesity management and metabolic disease. However, few studies have evaluated TBT effect on BAT function. In this investigation, we assessed whether subacute (15 days) and low dose of TBT exposure (100 ng/kg/day) results in abnormal BAT morphophysiology in adult male rats. Body temperature, BAT morphology, inflammation, oxidative stress, collagen deposition and BAT metabolic gene expression markers were assessed in room temperature (Room, â¼24 ºC) and after cold tolerance test (Cold, â¼4 ºC) conditions. A reduction in body temperature was observed in both Room and Cold conditions in TBT rats, suggesting abnormal BAT thermogenic function. Changes in BAT morphology were observed in TBT rats, with an increase in BAT lipid accumulation, an increase in BAT unilocular adipocyte number and a decrease in BAT multilocular adipocyte number in Room condition. All these parameters were opposite in Cold condition TBT rats, leading to a borderline increase in BAT UCP1 protein expression. An increase in BAT mast cell number was observed in TBT rats in Room condition. An increase in ED1 protein expression (macrophage marker) was observed in TBT rats in Cold condition. Oxidative stress and collagen deposition increased in both Room and Cold conditions in TBT rats. TBT exposure caused a borderline increase in BAT COL1A1 protein expression in Cold condition. Further, strong negative correlations were observed between body temperature and BAT lipid accumulation, and BAT lipid accumulation and multilocular adipocyte number. Thus, these data suggest that TBT exposure impaired BAT morphophysiology through impacts on lipid accumulation, inflammation, fibrosis and oxidative stress in male rats.
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Tejido Adiposo Pardo , Obesidad , Ratas , Masculino , Animales , Obesidad/metabolismo , Tejido Adiposo Pardo/metabolismo , Inflamación/metabolismo , Colágeno/metabolismo , LípidosRESUMEN
A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.
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Dieta , Insulinas , Ratas , Femenino , Animales , Inflamación , Fibrosis , Glucógeno , Glucosa , Dieta Alta en GrasaRESUMEN
The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng-20 ng/ml) and in vivo (10 ng-20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction.
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Compuestos de Trialquiltina , Animales , Femenino , Gónadas , Sistema Hipotálamo-Hipofisario , Hipotálamo , Mamíferos , Hipófisis , Reproducción , Compuestos de Trialquiltina/toxicidadRESUMEN
Tributyltin (TBT) is a persistent organometallic pollutant widely used in several agricultural and industrial processes. TBT exposure is associated with various metabolic, reproductive, immune, and cardiovascular abnormalities. However, few studies have evaluated the effects of TBT on behavior. In the present study, we aimed to investigate whether TBT exposure results in oxidative, neuroendocrine, and behavioral alterations. TBT was administered to adult female mice (250, 500, or 750 ng/kg/day or veh for 14 days), and their recognition memory was assessed. We have also evaluated estrogen receptor (ER)α protein expression and oxidative stress (OS) in brain areas related to memory, as well as the correlation between them. A reduction in short- and long-term recognition memory (STM and LTM) performance, as well as in total exploration time was observed in TBT mice. Reduced ERα protein expression was observed in the prefrontal cortex (PFC) and hippocampus of TBT mice, while an increase in TBARS concentration was observed in the PFC of treated animals. Collectively, these data suggest that TBT exposure impairs recognition memory in female mice as a result of, at least in part, its toxicological effects on ERα expression and OS in specific brain areas related to memory.
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Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for development of complications later in life and in subsequent generations. We previously demonstrated that exposure to the EDC organotin (OT), which is present in contaminated seafood, resulted in reproductive abnormalities in female rats. However, few studies have explored the effect of OT accumulation in seafood on pregnancy outcomes. This led us to consider the potential effects of the OT present in seafood on fertility, pregnancy, the placenta, and the offspring. In this investigation, we assessed whether exposure to the OT in contaminated seafood resulted in abnormal fertility and pregnancy features and offspring complications. OT in contaminated seafood (LNI) was administered to female rats, and their fertility, pregnancy outcomes, and fetal liver morphology were assessed. LNI caused abnormal fertility, a reduction in the total number of pups, and an increase in serum testosterone levels compared to controls. Furthermore, LNI exposure caused irregular uterine morphology with inflammation and fibrosis and led to a reduction in embryonic implantation. In pregnant rats, LNI caused abnormal lipid profiles and livers with steatosis features. LNI exposure also causes placental morpho-physiology disruption, a high presence of glycogen and inflammatory cells, and irregular lipid profiles. In addition, LNI exposure caused an increase in large amounts of carbohydrate and lipid delivery to the fetus via an increase in placental nutrient sensor protein expressions (GLUT1, IRß/mTOR and Akt). In both genders of offspring, LNI exposure led to an increase in body weights, liver megakaryocytes, lipid accumulation, and oxidative stress (OS) levels. Collectively, these data suggest that OT exposure from contaminated seafood in female rats leads to reduced fertility, uterine implantation failure, pregnancy and placental metabolic outcome irregularities, offspring adiposity, liver steatosis, and an increase in OS. Furthermore, some of the effects of OT may be the result of obesogenic and multigenerational effects of OT in adult female rats.
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Hígado Graso , Compuestos Orgánicos de Estaño , Animales , Femenino , Fertilidad , Masculino , Placenta , Embarazo , Resultado del Embarazo , RatasRESUMEN
Glyphosate (GLY) is a broad-spectrum, post-emergent, non-selective and synthetic universal herbicide, whose commercial formulations are referred to as glyphosate-based-herbicides (GBHs). These chemicals and their metabolites can be found in soil, air, water, as well as groundwater and food products. This review summarizes to summarize current in vitro and epidemiological studies investigating the effects of GLY exposure on human health. Recent human cell studies have reported several GLY and GBH toxicological effects and have contributed to a better understanding of the deleterious consequences associated with their exposure. However, these detrimental effects are dependent on the cell type, chemical composition, as well as magnitude and time of exposure, among other factors. Moreover, the deleterious effects of GLY exposure on human health were observed in epidemiological studies; however, most of these studies have not determined the GLY dosage to confirm a direct effect. While GLY toxicity is clear in human cells, epidemiological studies investigating individuals exposed to different levels of GLY have reported contradictory data. Therefore, based on currently available in vitro and epidemiological data, it is not possible to confirm the complete safety of GLY use, which will require additional comprehensive studies in animal models and humans.
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Glicina/análogos & derivados , Animales , Glicina/toxicidad , Herbicidas , Humanos , GlifosatoRESUMEN
Food Microbiology is included in majors such as Food Engineering, Food Science and Technology, Nutrition, Veterinary Medicine, Gastronomy, Pharmaceutical Sciences, among others. Food safety and hygiene are usually the focus, but the technological applications of microbes through fermentations are also covered. During an education symposium at the Brazilian Congress of Microbiology in 2017, a group of professors expressed their difficulties associated with teaching to new generations, the use of technology in the classroom, and the application of new learning tools. The objective of this study was to gather information about the educational practices among Brazilian professors who teach Food Microbiology throughout the country. The results indeed confirmed the diversity of careers in which food microbiology is taught. We verified that professors mixed traditional teaching strategies with modern active learning methods, even though some difficulties associated with lack of time, pedagogical training, and low adherence of students for adopting these modern methods were commonly highlighted. The preferred teaching approaches were dialogued or discussed lectures, seminars, homework, case studies, and field visits. It is noteworthy that most professors still use traditional teaching methods. It is crucial that awareness concerning the educational needs in different careers and the challenges and dilemmas facing education for the new generations should be dealt with by using effective teaching approaches in food microbiology education. We suggest that a more permanent discussion forum among faculty members dealing with food microbiology in the country should be launched and this work is a step towards this goal.
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Microbiología de Alimentos/educación , Brasil , Educación/métodos , Humanos , Enseñanza , UniversidadesRESUMEN
Mercury (Hg) is a heavy metal and Hg exposure is associated with various neural, immune, and cardiovascular abnormalities. However, few studies have evaluated Hg's toxicologic effect on reproductive and metabolic functions. In this study, we assessed whether Hg exposure results in reproductive and metabolic abnormalities. Hg was administered to adult female Wistar rats, mimicking the Hg levels found in exposed human blood, and their reproductive and metabolic function was assessed. Rats exposed to Hg displayed abnormal estrous cyclicity and ovarian follicular development, with a reduction in ovarian antral follicles and an increase in atretic and cystic ovarian follicles. Uterine atrophy with the presence of inflammatory cells was observed in Hg-exposed rats. The presence of abnormal ovarian fat accumulation, as well as increased ovarian lipid drops accumulation, was observed in Hg-exposed rats. Ovarian oxidative stress was also present in the Hg-exposed rats. High fasting glucose levels, glucose, and insulin intolerance were observed in Hg-exposed rats. Thus, these data suggest that Hg exposure led to abnormal reproductive and metabolic features similar to those found in the polycystic ovary syndrome (PCOS) rat models.
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Mercurio/toxicidad , Síndrome del Ovario Poliquístico/inducido químicamente , Animales , Glucemia , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Ratas , Ratas WistarRESUMEN
There is an increase in the incidence of cardiovascular events such as myocardial infarction (MI) after menopause. However, the use of estrogen therapy (E2) remains controversial. The aim of this study was to evaluate the effects of E2, alone and combined with exercise training (ET), on cardiac function and remodeling in ovariectomized (OVX) rats after MI. Wistar female rats underwent ovariectomy, followed by MI induction were separated into five groups: S; MI; MI+ET; MI+E2; and MI+ET+E2. Fifteen days after MI or sham surgery, treadmill ET and/or estrogen therapy [17-ß estradiol-3-benzoate (E2), s.c. three times/week] were initiated and maintained for 8 weeks. After the treatment and/or training period, the animals underwent cardiac hemodynamic evaluation through catheterization of the left ventricle (LV); the LV systolic and diastolic pressures (LVSP and LVEDP, respectively), maximum LV contraction and relaxation derivatives (dP/dt+ and dP/dt-), and isovolumic relaxation time (Tau) were assessed. Moreover, histological analyses of the heart (collagen and hypertrophy), cardiac oxidative stress [advanced oxidation protein products (AOPPs)], pro- and antioxidant protein expression by Western blotting and antioxidant enzyme activity in the heart were evaluated. The MI reduced the LVSP, dP/dt+ and dP/dt- but increased the LVEDP and Tau. E2 did not prevent the MI-induced changes in cardiac function, even when combined with ET. An increase in the dP/dt+ was observed in the E2 group compared with the MI group. There were no changes in collagen deposition and myocyte hypertrophy caused by the treatments. The increases in AOPP, gp91-phox, and angiotensin II type 1 receptor expression induced by MI were not reduced by E2. There were no changes in the expression of catalase caused by MI or by the treatments, although, a reduction in superoxide dismutase (SOD) expression occurred in the groups subjected to E2 treatment. Whereas there were post-MI reductions in activities of SOD and catalase enzymes, only that of SOD was prevented by ET. Therefore, we conclude that E2 therapy does not prevent the MI-induced changes in cardiac function and worsens parameters related to cardiac remodeling. Moreover, E2 reverses the positive effects of ET when used in combination, in OVX infarcted female rats.
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Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by abnormal reproductive cycles, irregular ovulation, and hyperandrogenism. This complex disorder has its origins both within and outside the hypothalamic-pituitary-ovarian axis. Cardio-metabolic factors, such as obesity and insulin resistance, contribute to the manifestation of the PCOS phenotype. Polycystic ovary syndrome is one of the most common endocrine disorders among women of reproductive age. Growing evidence suggested an association between reproductive and metabolic features of PCOS and exposure to endocrine-disrupting chemicals (EDC), such as bisphenol A. Further, the environmental obesogen tributyltin (TBT) was shown to induce reproductive, metabolic and cardiovascular abnormalities resembling those found in women and animal models of PCOS. However, the causal link between TBT exposure and PCOS development remains unclear. The objective of this review was to summarize the most recent research findings on the potential association between TBT exposure and development of PCOS-like features in animal models and humans.
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Exposición a Riesgos Ambientales/análisis , Obesidad/inducido químicamente , Síndrome del Ovario Poliquístico/inducido químicamente , Compuestos de Trialquiltina/efectos adversos , Animales , Femenino , Humanos , Obesidad/patología , Obesidad/fisiopatología , Síndrome del Ovario Poliquístico/patología , Síndrome del Ovario Poliquístico/fisiopatologíaRESUMEN
Organotin compounds (OTs) are synthetic persistent organometallic xenobiotics widely used in several commercial applications. They exert well-described harmful effects in brain, liver, adipose tissue, and reproductive organs, as they are endocrine-disrupting chemicals (EDCs), but the effects in the kidneys are less known. The kidneys are especially vulnerable to environmental contaminants because they are a metabolizing site of xenobiotics, therefore, pollutants can accumulate in renal tissue, leading to impaired renal function and to several renal abnormalities. Individuals chronically exposed to OTs present a threefold increase in the prevalence of kidney stones. These compounds can directly inhibit H+/K+-ATPase in renal intercalated cells, resulting in hypokalemia, renal tubular acidity, and increased urinary pH, which is a known risk factor for kidney stones formation. OTs effects are not only limited to induce nephrolithiasis, its nephrotoxicity is also due to increased reactive oxygen species (ROS). This increase leads to lipid peroxidation, abnormal cellular function, and cell death. Combined, the enzymatic and non-enzymatic antioxidant defense systems become deficient and there is a consequent uncontrolled generation of ROS that culminates in renal tissue damage. Still, few epidemiological and experimental studies have reported renal impact correlated to OTs exposure. This lack of investigation of the complete effect of OTs in renal function and structure led us to perform this review reporting the main researches about this subject.
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Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-ß and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.
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Adipogénesis/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Adiposidad/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Obesidad/inducido químicamente , Ovario/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Adipogénesis/genética , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Tejido Adiposo/fisiopatología , Adiposidad/genética , Animales , Atrofia , Colesterol/metabolismo , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Ciclo Estral/sangre , Ciclo Estral/efectos de los fármacos , Femenino , Fibrosis , Regulación Enzimológica de la Expresión Génica , Hormonas Esteroides Gonadales/sangre , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Obesidad/metabolismo , Obesidad/patología , Obesidad/fisiopatología , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Folículo Ovárico/patología , Ovario/metabolismo , Ovario/patología , Ovario/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Enfermedad Inflamatoria Pélvica/inducido químicamente , Enfermedad Inflamatoria Pélvica/metabolismo , Enfermedad Inflamatoria Pélvica/patología , Enfermedad Inflamatoria Pélvica/fisiopatología , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas WistarRESUMEN
Osteoporosis is one of the major diseases that affects mostly postmenopausal women. Despite being a multifactorial disease, some genes have been shown to play an important role in osteoporosis. Bone mineral density (BMD) is still largely used to diagnose it, although many other biomarkers are used to better follow the disease onset. It has been shown that the apolipoprotein E (APOE) gene could be a biomarker for risk of fractures as well as to predict lower BMD in patients with osteoporosis. The human APOE gene encodes 3 protein isoforms called ApoE2, ApoE3, and ApoE4, resulting in 4 possible genotypes, because they are a product of a single nucleotide polymorphism found in this gene. So far, the APOE4 allele has been associated with low BMD in postmenopausal women and to incidence of bone breaking in older women. This study aimed to investigate the role of ApoE isoforms in a cohort of 413 postmenopausal Brazilian women. These patients were randomly recruited, clinically examined, and subjected to dual-energy X-ray absorptiometry to measure their BMD. Patients were further grouped as normal BMD (T-score < 0.5) or low BMD (T-score > 1.0, osteopenic or osteoporotic). Patients with osteopenia or osteoporosis were further genotyped for APOE alleles as well as tested for many serum bone turnover biomarkers. Our data showed that presence of the APOE3 allele was associated with both higher BMDs and higher serum concentrations of osteocalcin and alkaline phosphatase, biomarkers for bone formation. On the other hand, the APOE2 and APOE4 alleles were associated with lower BMD as well as higher levels of serum C-terminus collagen peptide and urinary deoxipyridinolines, biomarkers for bone resorption. However, these effects on lower BMD and bone resorption biomarkers observed in either APOE2 or APOE4 alleles were eliminated when patients' genotype carried the APOE3 allele. Codominance of the APOE3 allele was also associated with lesser cases of bone fractures in these patients within a 5-year follow-up. In conclusion, our data show that APOE4 may be associated with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas APOE3 seems to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone breaking in patients with osteoporosis.