RESUMEN
OBJECTIVES: This study was performed to investigate the protective effects of taurine (2-aminoethanesulfonic acid, TAU) on oxidative stress in the isolated mouse testicular mitochondria, mitochondrial membrane potential (MMP), viability and motility of the exposed sperms to the BPA. METHODS: We treated epididymal spermatozoa obtained from mice and isolated mouse testicular mitochondria with BPA (0.8 mmol/mL) and various doses of TAU (5, 10, 30 and 50 µmol/L). We used the MTT assay and Rhodamine 123 uptake to assess sperm viability and MMP. We assessed the oxidative stress through measuring ROS (reactive oxygen species), MDA (malondialdehyde), GSH (glutathione), and SOD (super-oxide dismutase) levels in the testicular mitochondrial tissue. RESULTS: BPA significantly elevated ROS, MDA and MMP levels, and markedly reduced SOD and GSH levels in the isolated mitochondria. BPA also considerably impaired spermatozoa viability and motility. Pretreatment with 30 and 50 µmol/L of TAU could considerably suppressed mitochondrial oxidative stress, enhanced MMP, and improved sperm motility and viability. CONCLUSION: TAU may attenuate the BPA-induced mitochondrial toxicity and impaired sperm motility via decreasing oxidative stress.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Estrógenos no Esteroides/toxicidad , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Sustancias Protectoras/farmacología , Motilidad Espermática/efectos de los fármacos , Taurina/farmacología , Testículo/efectos de los fármacos , Animales , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Superóxido Dismutasa/metabolismo , Testículo/metabolismoRESUMEN
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200â¯nM BPA for 2â¯h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Células del Cúmulo/fisiología , Estrógenos no Esteroides/toxicidad , Uniones Comunicantes/fisiología , Oocitos/fisiología , Oogénesis/fisiología , Fenoles/toxicidad , Animales , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Células del Cúmulo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Uniones Comunicantes/efectos de los fármacos , Meiosis/efectos de los fármacos , Meiosis/fisiología , Ratones , Ratones Endogámicos C57BL , Oocitos/efectos de los fármacos , Oogénesis/efectos de los fármacosRESUMEN
Bisphenol A (BPA) is a synthetic non-steroidal oestrogen used in the production of plastics. BPA can cause alterations in the endocrine system of human beings and animals at varied stages of development. During puberty, altered morphological, sexual behaviour and completion of the epididymal development occur. Therefore, this study aimed to evaluate the effects of BPA on epididymal development during the peripubertal period of rats. Male Wistar rats were treated with BPA via gavage at doses of 20 µg/kg or 200 µg/kg per day [post-natal day (PND] 36-66). The control group received the vehicles under the same conditions. Feed and water were provided ad libitum. On PND 67, the epididymis was removed, weighed, divided into caput/corpus and cauda sections. It was then used for sperm count determination; histopathological and stereological evaluation; inflammatory cell enzymatic profiling (myeloperoxidase activity - MPO; N-acetylglucosaminidase - NAG); immunohistochemistry for IL-6; and evaluation of superoxide anion levels and malondialdehyde (MDA). Exposure to BPA at 200 µg/kg caused a significant increase of MPO activity and immunoreactivity to IL-6 (interleukin-6) as well as remodelling of tissue components in the caput/corpus and cauda regions of the epididymis. Under these experimental conditions, it is concluded that BPA alters post-natal epididymal development.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Epidídimo/efectos de los fármacos , Estrógenos no Esteroides/toxicidad , Mediadores de Inflamación/metabolismo , Fenoles/toxicidad , Acetilglucosaminidasa/metabolismo , Factores de Edad , Animales , Relación Dosis-Respuesta a Droga , Epidídimo/metabolismo , Epidídimo/patología , Interleucina-6/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Tamaño de los Órganos , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas Wistar , Desarrollo Sexual , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Superóxidos/metabolismoRESUMEN
Bisphenol A (BPA) and cadmium (Cd) are environmental pollutants that are implicated in potential reproductive effects, including damage to the prostate gland. Their action during puberty requires analysis to determine the relationship of these compounds with the testosterone peak that occurs during this phase. This study evaluated whether exposure to BPA and Cd during puberty can cause changes in the morphology, proliferation and cell death and androgen receptor (AR) immunostaining of the ventral prostates of normal and castrated male gerbils (Meriones unguiculatus), considering an acute exposure to the chemicals and evaluation after short (52d) and long (120d) periods. Generally, morphometric-stereological results demonstrated that administration of BPA and Cd (individually or in combination) increased epithelial height, smooth muscle layer (SML) thickness and nuclear area and perimeter, and that these parameters were reduced in castrated animals. In addition, these groups showed important inflammatory processes but not prostate lesions. The proliferation/death rates of prostatic cells obtained by PCNA and TUNEL immunostaining demonstrated increased cell death in the 52d groups; in contrast, the gland acquired a more proliferative nature in the 120d groups. AR immunostaining showed that BPA and Cd compounds interact with ARs in different ways depending on the evaluated period and the hormonal profile of the animal. We conclude that BPA and cadmium are important agents in changing the morphology, proliferation and death of prostatic cells, in addition to interacting with ARs in different patterns. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 48-61, 2017.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Cadmio/toxicidad , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Próstata/patología , Andrógenos/farmacología , Animales , Fragmentación del ADN/efectos de los fármacos , Gerbillinae , Inmunohistoquímica , Masculino , Orquiectomía , Próstata/efectos de los fármacos , Receptores Androgénicos/efectos de los fármacos , Testosterona/sangreAsunto(s)
Compuestos de Bencidrilo/toxicidad , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Genisteína/toxicidad , Indoles/toxicidad , Glándulas Mamarias Animales/efectos de los fármacos , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Animales , Anticarcinógenos/toxicidad , Compuestos de Bencidrilo/administración & dosificación , Estrógenos no Esteroides/toxicidad , Femenino , Genisteína/administración & dosificación , Indoles/administración & dosificación , Glándulas Mamarias Animales/crecimiento & desarrollo , Glándulas Mamarias Animales/patología , Fenoles/administración & dosificación , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/patología , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
The study of oral exposure to the environmental estrogen bisphenol A (BPA) during the perinatal period and its effects on ovarian functionality in adulthood has generated special interest. Thus, our objective was to investigate ovarian folliculogenesis and steroidogenesis in adult female rat offspring born to mothers exposed to low doses of BPA (BPA50: 50µg/kgday; BPA0.5: 0.5µg/kgday) by the oral route during gestation and breastfeeding. Ovaries from both BPA-treated groups showed reduced primordial follicle recruitment and a greater number of corpora lutea, indicating an increased number of ovulated oocytes, coupled with higher levels of mRNA expression of 3ß-hydroxysteroid dehydrogenase and serum progesterone. BPA50-treated animals had lower expression of androgen receptor (AR) at different stages of the growing follicle population. BPA0.5-treated rats evidenced an imbalance of AR expression between primordial/primary follicles, with higher mRNA-follicle-stimulating hormone receptor expression. These results add to the growing evidence that folliculogenesis and steroidogenesis are targets of BPA within the ovary.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Estrógenos no Esteroides/toxicidad , Ovario/efectos de los fármacos , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal , 3-Hidroxiesteroide Deshidrogenasas/genética , Animales , Estradiol/sangre , Femenino , Intercambio Materno-Fetal , Madres , Tamaño de los Órganos/efectos de los fármacos , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Embarazo , Progesterona/sangre , ARN Mensajero/metabolismo , Ratas Wistar , Receptores Androgénicos/metabolismoRESUMEN
Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 µg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (â¼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.
Asunto(s)
Suplementos Dietéticos , Estrógenos no Esteroides/antagonistas & inhibidores , Genisteína/uso terapéutico , Fenómenos Fisiologicos Nutricionales Maternos , Fitoestrógenos/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/prevención & control , Próstata/efectos de los fármacos , Animales , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/antagonistas & inhibidores , Compuestos de Bencidrilo/toxicidad , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estrógenos no Esteroides/administración & dosificación , Estrógenos no Esteroides/toxicidad , Femenino , Masculino , Fenoles/administración & dosificación , Fenoles/antagonistas & inhibidores , Fenoles/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Hiperplasia Prostática/prevención & control , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Organismos Libres de Patógenos Específicos , DesteteRESUMEN
The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.
Asunto(s)
Estrógenos no Esteroides/toxicidad , Zearalenona/toxicidad , Animales , Linfocitos B/inmunología , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Eritrocitos/inmunología , Femenino , Inmunoglobulina M/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Tamaño de los Órganos/efectos de los fármacos , Ovariectomía , Ratas , Ratas Wistar , Ovinos , Bazo/efectos de los fármacos , Bazo/crecimiento & desarrollo , Timo/efectos de los fármacos , Timo/patología , Útero/efectos de los fármacos , Útero/crecimiento & desarrolloRESUMEN
Successful implantation is the result of complex molecular interactions between the hormonally primed uterus and a mature blastocyst. This very carefully synchronized interplay of hormonal signals and feedback loops is potentially vulnerable to chemicals such as endocrine disruptors that may disrupt endocrine signaling. Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. This chapter describes the effects of brief postnatal exposure to BPA on female reproductive performance and specifically on the uterine adaptations during the preimplantation period. We propose that an early alteration in Hoxa10 gene expression affects the functional differentiation of the preimplantation uterus as part of an altered endocrine signal transduction pathway. These molecular alterations could explain, at least in part, the adverse effects of BPA on uterine implantation. Exposure to endocrine disruptors, such as BPA, could contribute to the impaired female fertility noted over the past decades.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Implantación del Embrión/efectos de los fármacos , Pérdida del Embrión/inducido químicamente , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Fenoles/toxicidad , Útero/efectos de los fármacos , Animales , Animales Recién Nacidos , Desarrollo Infantil/efectos de los fármacos , Pérdida del Embrión/patología , Pérdida del Embrión/fisiopatología , Estrógenos no Esteroides/toxicidad , Femenino , Humanos , Recién Nacido , Infertilidad Femenina/etiología , Embarazo , Útero/patologíaRESUMEN
The hypothalamic-growth hormone (GH)-liver axis represents a new concept in endocrine regulation of drug toxicity. Preponderant sex differences are found in liver gene expression, mostly dependent on the sexually dimorphic pattern of GH secretion which is set during the neonatal period by gonadal steroids. We tested if GH-dependent sexually dimorphic liver enzymes and proteins was perturbed by neonatal Bisphenol A (BPA) treatment in female rats. Female rats were sc injected with BPA (50 or 500 µg/50 µl) or castor oil vehicle from postnatal day 1 to 10. At five months serum prolactin, pituitary GH, and serum and liver insulin growth factor-I (IGF-I) were measured by RIA. Major urinary proteins (MUPs) were determined by electrophoresis. Liver Cyp2c11, Cyp2c12, Adh1, Hnf6, and Prlr mRNA levels were determined by real time PCR. Pituitary GH content and liver IGF-I concentration were increased by neonatal BPA treatment, indicating partial masculinization of the GH axis in treated females. GH-dependent female predominant liver enzyme genes (Cyp2c12 and Adh1) and a transcription factor (Hnf6) were downregulated or defeminized, while there were no changes in a male predominant gene (Cyp2c11) or protein (MUP). Our findings indicate that perinatal exposure to BPA may compromise the sexually dimorphic capacity of the liver to metabolize drugs and steroids.
Asunto(s)
Disruptores Endocrinos/toxicidad , Estrógenos no Esteroides/toxicidad , Hormona del Crecimiento/metabolismo , Hígado/efectos de los fármacos , Fenoles/toxicidad , Hipófisis/efectos de los fármacos , Factores de Edad , Envejecimiento/genética , Envejecimiento/metabolismo , Alcohol Deshidrogenasa/genética , Animales , Animales Recién Nacidos , Hidrocarburo de Aril Hidroxilasas/genética , Compuestos de Bencidrilo , Familia 2 del Citocromo P450 , Esquema de Medicación , Electroforesis en Gel de Poliacrilamida , Disruptores Endocrinos/administración & dosificación , Estrógenos no Esteroides/administración & dosificación , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Factor Nuclear 6 del Hepatocito/genética , Inyecciones Subcutáneas , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hígado/metabolismo , Masculino , Fenoles/administración & dosificación , Hipófisis/metabolismo , Prolactina/sangre , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Prolactina/genética , Caracteres Sexuales , Factores Sexuales , Esteroide 16-alfa-Hidroxilasa/genética , Esteroide Hidroxilasas/genéticaRESUMEN
Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium, commonly found in the soil in temperate and warm countries and is a frequent contaminant of cereal crops worldwide. Accordingly, it has been implicated in several mycotoxicosis in farm animals and in humans, but the underlying mechanisms remain largely unknown. Therefore, the current study was aimed to investigate the effect of an acute dose of ZEA (40 mg/kg, p.o.) on reproductive and hematological parameters, as well as on markers of oxidative stress in liver, kidney and testes in mice. Adult Swiss albino male mice were exposed to a single oral administration of ZEA, and 48 h thereafter behavioral and biochemical tests were performed. No differences in locomotor or exploratory activity were observed in the open-field test. On the other hand, ZEA increased the number of leukocytes, segmented neutrophils, sticks, eosinophils, monocytes and decreased platelets and lymphocytes number. Moreover, ZEA drastically reduced the number and motility of live spermatozoa. Additionally, while levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH) and ascorbic acid in liver, kidney and testes were not altered by ZEA administration, superoxide dismutase activity increased in all tissues evaluated, catalase activity increased in the kidney, and glutathione-S-transferase activity decreased in kidney and testes. In summary, we showed that ZEA have acute toxic effects mainly in reproductive system of adult male Swiss albino mice and its effect probably is related to a reduced activity of GST and increased in SOD activity in testes.
Asunto(s)
Modelos Animales de Enfermedad , Estrógenos no Esteroides/toxicidad , Glutatión Transferasa/metabolismo , Micotoxicosis/enzimología , Oligospermia/enzimología , Testículo/efectos de los fármacos , Zearalenona/toxicidad , Animales , Catalasa/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Fusarium/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Especificidad de Órganos , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Superóxido Dismutasa/metabolismo , Testículo/enzimología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor ß subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr(308) residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor ß subunit.In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes.
Asunto(s)
Metabolismo Energético/efectos de los fármacos , Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Animales , Compuestos de Bencidrilo , Glucosa/metabolismo , Inyecciones Subcutáneas , Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor de Insulina/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129µM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
Asunto(s)
Antidepresivos de Segunda Generación/toxicidad , Estrógenos no Esteroides/toxicidad , Fluoxetina/toxicidad , Receptores de Estrógenos/metabolismo , Útero/efectos de los fármacos , Animales , Línea Celular Tumoral , Femenino , Genitales Masculinos/anatomía & histología , Genitales Masculinos/efectos de los fármacos , Humanos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Útero/patologíaRESUMEN
We hypothesized that neonatal xenoestrogen exposure affects the ovarian follicular dynamics in lambs. Female lambs were exposed from postnatal day (PND) 1-14 to low doses of diethylstilbestrol (DES) or bisphenol A (BPA). At PND 30, the follicular dynamics and ovarian biomarkers (ERα, ERß, AR, Ki67, p27) were evaluated. Lambs exposed to DES or BPA showed a decline in the stock of primordial follicles with stimulation of follicular development. BPA reduced ovarian weight and increased the number of multioocyte follicles. BPA promoted proliferation of granulosa/theca cells in antral follicles, and increased both the number of antral atretic follicles and p27 expression. Neonatal exposure to BPA or DES reduced the primordial follicle pool by stimulating their initial recruitment and subsequent follicle development until antral stage. In prepubertal lambs, the accelerated folliculogenesis resulted in increased incidence of atretic follicles. These alterations may affect the ovarian function in the adult.
Asunto(s)
Dietilestilbestrol/toxicidad , Estrógenos no Esteroides/toxicidad , Folículo Ovárico/efectos de los fármacos , Fenoles/toxicidad , Animales , Animales Recién Nacidos , Compuestos de Bencidrilo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Femenino , Antígeno Ki-67/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Folículo Ovárico/metabolismo , Folículo Ovárico/patología , Ovario/efectos de los fármacos , Ovario/crecimiento & desarrollo , Receptores Androgénicos/metabolismo , Oveja DomésticaRESUMEN
Bisphenol A (BPA) is an estrogenic agonist compound that induces changes in diverse reproductive parameters in rats. The aim of the present study was to determine the effects of BPA given in drinking water containing 10mg/L (approximate dose 1.2mg/kg BW/day), administered chronically to rats during pregnancy and lactation, on reproductive tract parameters of the offspring. 79.2% of the female offspring from BPA-treated mothers presented irregular estrous cycles. As compared to the control group, a significant increase in the thickness of the uterine epithelia and stroma was observed in the BPA group. Additionally, 60% of the female offspring from BPA mothers did not undergo abundant uterine epithelial apoptosis during the estrus phase of the cycle while control animals did. In addition, a down regulation of ERα expression was observed in epithelial cells on estrus day. The results indicate that BPA, when administered chronically in water beverages to dams, modifies the reproductive cycle of the offspring during young adulthood.
Asunto(s)
Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal , Reproducción/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Compuestos de Bencidrilo , Epitelio/anatomía & histología , Epitelio/química , Epitelio/efectos de los fármacos , Receptor alfa de Estrógeno/análisis , Estrógenos no Esteroides/administración & dosificación , Ciclo Estral/efectos de los fármacos , Femenino , Lactancia , Fenoles/administración & dosificación , Embarazo , Ratas , Ratas Wistar , Reproducción/fisiología , Útero/anatomía & histología , Útero/química , Útero/efectos de los fármacos , AguaRESUMEN
We evaluated whether exposure to bisphenol A (BPA) disrupts neonatal follicle development in rats. From postnatal day 1 (PND1) to PND7, pups received corn oil (control), diethylstilbestrol (DES20: 20 µg/kg-d, DES0.2: 0.2 µg/kg-d), or BPA (BPA20: 20mg/kg-d, BPA0.05: 0.05 mg/kg-d). We examined follicular dynamics, multioocyte follicles (MOFs) incidence, proliferation and apoptosis rates, expression of steroid receptors (ERα, ERß, PR, AR) and cyclin-dependent kinase inhibitor 1B (p27) in PND8 ovaries. DES20, DES0.2 and BPA20-ovaries showed fewer primordial follicles and increased growing follicles. DES20-ovaries exhibited increased incidence of MOFs. Oocyte survival, AR, PR and apoptosis were not changed. Primordial and recruited follicles from BPA20-ovaries showed higher p27, whereas ERß and proliferation were both increased in recruited follicles. ERα positive primary follicles increased in BPA 20-ovaries. Results show that BPA reduces the primordial follicle pool by stimulating the neonatal initial recruitment, associated with an increased proliferation rate likely mediated by an estrogenic pathway.
Asunto(s)
Disruptores Endocrinos/toxicidad , Estrógenos no Esteroides/toxicidad , Células Germinativas/efectos de los fármacos , Oogénesis/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/crecimiento & desarrollo , Fenoles/toxicidad , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Compuestos de Bencidrilo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Relación Dosis-Respuesta a Droga , Disruptores Endocrinos/administración & dosificación , Estrógenos no Esteroides/administración & dosificación , Femenino , Células Germinativas/crecimiento & desarrollo , Células Germinativas/metabolismo , Células Germinativas/patología , Folículo Ovárico/metabolismo , Folículo Ovárico/patología , Fenoles/administración & dosificación , Insuficiencia Ovárica Primaria/inducido químicamente , Isoformas de Proteínas/metabolismo , Ratas , Ratas Wistar , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: Early-life exposures to hormonally active compounds and other factors may affect later response to estrogen or progesterone and hence may influence development of uterine leiomyomata (fibroids). OBJECTIVES: We evaluated associations of in utero and early-life exposures, including soy formula, with self-report of physician-diagnosed fibroids by 35 years of age. METHODS: Our study included 19,972 non-Hispanic white women who were 35-59 years of age when they enrolled in the Sister Study in 20032007. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using log-binomial regression models for fibroid associations with adjustment for participant's age and education, maternal age at participant's birth, birth order, and childhood family income. RESULTS: Greater risk of early fibroid diagnosis was associated with soy formula during infancy (RR = 1.25; 95% CI, 0.971.61), maternal prepregnancy diabetes (RR = 2.05; 95% CI, 1.163.63), low childhood socioeconomic status (RR = 1.28; 95% CI, 1.011.63), and gestational age at birth (RR = 1.64; 95% CI, 1.272.13, for being born at least 1 month early). In utero diethylstilbestrol (DES) exposure was also associated with early fibroid diagnosis (RR = 1.42; 95% CI, 1.131.80), but this association was driven by women reporting probable rather than definite exposure. CONCLUSIONS: There are plausible biological pathways by which these early-life factors could promote fibroid pathogenesis. This is the first epidemiologic study to evaluate such exposures, with the exception of in utero DES, in relation to fibroid risk, and replication of findings in other populations is needed.
Asunto(s)
Dietilestilbestrol/toxicidad , Estrógenos no Esteroides/toxicidad , Leiomioma/diagnóstico , Leiomioma/etiología , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/etiología , Hermanos , Adulto , Edad de Inicio , Diabetes Gestacional , Femenino , Humanos , Fórmulas Infantiles , Recién Nacido , Recien Nacido Prematuro , Leiomioma/inducido químicamente , Leiomioma/epidemiología , Exposición Materna/estadística & datos numéricos , Persona de Mediana Edad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Puerto Rico/epidemiología , Factores Socioeconómicos , Glycine max , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Estrogenic activity of kraft pulp mill effluents (P. radiata, E. globulus and mixed -50% E. globulus and 50% P. radiata) was evaluated by the yeast estrogen screen assay. The estrogenic activity values were relatively low, ranking between 1.475 and 0.383 ng/L of EE2 eq. (Estrogenic equivalent of 17 alpha-ethynylestradiol), where the highest value corresponds to the E. globulus effluent and the lowest value to the P. radiata effluent. Analysis by solid phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) of chemical compounds present in all three effluents detected at least five major groups of organic compounds, corresponding to fatty acids, hydrocarbons, phenols, sterols and triterpenes. Comparison of analytical and biological data suggests that sterols could be the cause of the estrogenic activity in the evaluated effluent.
Asunto(s)
Disruptores Endocrinos/toxicidad , Estrógenos no Esteroides/toxicidad , Residuos Industriales/análisis , Papel , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Contaminantes Químicos del Agua/toxicidad , Disruptores Endocrinos/análisis , Estrógenos no Esteroides/análisis , Etinilestradiol/toxicidad , Eucalyptus , Cromatografía de Gases y Espectrometría de Masas , Oxígeno/análisis , Pinus , Extracción en Fase Sólida , Esteroles/análisis , Esteroles/toxicidad , Triterpenos/análisis , Triterpenos/toxicidad , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisisRESUMEN
Hormonally controlled vascular changes play a key role in endometrial development and in the differentiation process necessary for implantation. Vascular endothelial growth factor (VEGF) has emerged as one of the central regulators of the uterine vasculature. Hormonal perturbations during neonatal development may alter sex steroid-dependent regulation of VEGF and may ultimately affect fertility later in life. The aim of this study was to determine whether neonatal exposure to the environmental estrogenic chemical bisphenol A (BPA) affects the adult rat uterine response to hormonal stimuli. Newborn female rats were given s.c. injections of vehicle, BPA (0.05 mg/kg per day or 20 mg/kg per day) or diethylstilbestrol (0.2 microg/kg per day) on Postnatal Days 1, 3, 5, and 7. To evaluate the long-term effects, rats were ovariectomized at Postnatal Day 80 and submitted to hormonal replacement. Rats neonatally exposed to xenoestrogens showed a decreased induction of uterine endothelial proliferation and a decreased Vegf mRNA expression in response to ovarian steroid treatment. Also, although the estrogen receptor alpha (ESR1) expression was lower in subepithelial cells than in controls, a higher expression of silencing mediator of retinoic acid and thyroid hormone receptor (NCOR1, also known as SMRT) corepressor was evidenced in the same compartment. The results indicate that disturbed Vegf expression in BPA rats could be the result of changes in endocrine pathways, such as an altered induction of ESR1 and/or NCOR1 expression. Because of the importance of VEGF in the implantation process, our data suggest that neonatal BPA exposure might have negative consequences on female fertility.
Asunto(s)
Disruptores Endocrinos/toxicidad , Endotelio Vascular/efectos de los fármacos , Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Útero/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Animales Recién Nacidos , Compuestos de Bencidrilo , Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Estradiol/metabolismo , Receptor alfa de Estrógeno/metabolismo , Femenino , Neovascularización Fisiológica/efectos de los fármacos , Ovariectomía , Progesterona/metabolismo , Ratas , Ratas Endogámicas , Receptores de Progesterona/metabolismo , Útero/irrigación sanguínea , Útero/metabolismoRESUMEN
The estrogenic activity of environmentally relevant doses of endosulfan was investigated using an animal model. Ovariectomized adult rats were injected once a day for 3 days with sesame oil (control), 0.02mg/kg/day 17beta-estradiol (an uterotrophic dose; UE(2)), 0.0002mg/kg/day 17beta-estradiol (a non-uterotrophic dose; NUE(2)), or 0.006, 0.06, 0.6 or 6mg/kg/day endosulfan. After 24h of treatment, the uteri were weighed (uterotrophic assay) and the luminal epithelial cell height (LECH) and progesterone receptor (PR), and estrogen receptor alpha (ERalpha) protein levels were measured. PR, ERalpha, and complement factor-3 (C3) mRNAs were evaluated using real-time PCR. Uterine weight and LECH were only increased in UE(2)-treated rats. PR, ERalpha and C3 expression levels were modified in most of the endosulfan-treated groups, showing an identical pattern of expression to the NUE(2)-group. Our results show that the pesticide endosulfan mimics non-uterotrophic E(2) actions, strengthening the hypothesis that endosulfan is a widespread xenoestrogen.