RESUMEN
Over 50% of the causes of fetal malformations in humans are still unknown. Recent evidence suggests the relationship between environmental exposure to endocrine disruptors and fetal malformations. Our study aims to establish the role of Bisphenol A (BPA), if any, in altering human reproduction. We enrolled 151 pregnant women who were divided into two groups: case group (CS, n=101), women with established diagnosis of developmental defect, and control group (CL, n=50), pregnant women with normally developed fetus. Total, free and conjugated BPA were measured in their blood using GC-MS with isotopic dilution. The results show a correlation between environmental exposure to BPA and the genesis of fetal malformations. Conjugated BPA, which was higher in the CL, casts light on the hypothesis that a reduced ability to metabolize the chemical in the mother can concur to the occurrence of malformation. In a more detailed manner, in case of chromosomal malformations, the average value of free BPA appears to be nearly three times greater than that of the controls. Similarly, in case of central and peripheral nervous system non-chromosomal malformations, the value of free BPA is nearly two times greater than that of the controls.
Asunto(s)
Compuestos de Bencidrilo/envenenamiento , Anomalías Congénitas/etiología , Feto/efectos de los fármacos , Exposición Materna/efectos adversos , Fenoles/envenenamiento , Adulto , Compuestos de Bencidrilo/sangre , Aberraciones Cromosómicas/efectos de los fármacos , Anomalías Congénitas/sangre , Estrógenos no Esteroides/sangre , Estrógenos no Esteroides/envenenamiento , Femenino , Feto/anomalías , Cromatografía de Gases y Espectrometría de Masas , Humanos , Fenoles/sangre , EmbarazoRESUMEN
A method was established for the determination of three phenolic environmental estrogens, namely bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP), in urine from women of uterine leiomyoma group (n=49) and control group (n=29), by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urine samples were spiked with 2,4,6-tribromophenyl-terminated tetrabromobisphenol-A carbonate oligomer (TBBPA) and nonylphenol D8 (NP-D8) as internal standard (I.S.) and de-conjugated by adding ß-glucuronidase and sulfatase before the SPE. The extraction recoveries of BPA, NP and OP were more than 73.3%; the standard curve was linear over the validated concentrations in the range of 1.0-100.0ng/mL and the limits of detection (LOD) of BPA, NP and OP were 0.32ng/mL, 0.18ng/mL and 0.15ng/mL, respectively. Moreover, by analysing quality control urine samples in 5 days, the results showed that the method was precise and accurate, for the intra- and inter-day CV% within 15.2%. Except that OP was not found (
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Estrógenos no Esteroides/orina , Leiomioma/orina , Fenoles/orina , Espectrometría de Masas en Tándem/métodos , Neoplasias Uterinas/orina , Adulto , Estudios de Casos y Controles , Estabilidad de Medicamentos , Estrógenos no Esteroides/envenenamiento , Femenino , Humanos , Leiomioma/inducido químicamente , Límite de Detección , Modelos Lineales , Persona de Mediana Edad , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Neoplasias Uterinas/inducido químicamenteRESUMEN
BACKGROUND: Obesity is associated with an increased risk of estrogen-dependent breast cancer. Recently, concerns have been raised regarding the role of zeranol (Z), a non-steroidal anabolic growth promoter with potent estrogenic activity widely used in the U.S.A. beef industry, as a possible contributor to an increased incidence of human breast cancer. This study hypothesized that obese individuals may be at greater risk of developing zeranol-induced breast cancer. MATERIALS AND METHODS: The aromatase mRNA expression level of three cell types isolated from adipose tissues were assayed by RT-PCR, and the cell proliferation of primary cultured human normal breast pre-adipocytes (HNBPADs) was investigated using the CellTiter96® non-radioactive method. The effects of Z and gossypol on aromatase expression of leptin-pretreated HNBPADs were evaluated by RT-PCR. RESULTS: HNBPADs expressed higher aromatase than primary cultured human breast epithelial cells and stromal cells. Z enhanced the mitogenic activity of leptin and increased aromatase expression in HNBPADs. Moreover, (-)-gossypol counteracted Z- and leptin-induced cell proliferation and aromatase expression. CONCLUSION: These results suggested that bioactive Z metabolites contained in meat produced from Z-implanted beef cattle may increase estrogen biosynthesis in obese individuals by increasing aromatase expression and estrogen production, which will promote cell sensitivity and increase breast cancer cell growth.
Asunto(s)
Adipocitos/efectos de los fármacos , Aromatasa/biosíntesis , Neoplasias de la Mama/enzimología , Mama/efectos de los fármacos , Gosipol/farmacología , Leptina/farmacología , Zeranol/farmacología , Adipocitos/citología , Adipocitos/enzimología , Aromatasa/genética , Mama/citología , Mama/enzimología , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Procesos de Crecimiento Celular/efectos de los fármacos , Estrógenos no Esteroides/farmacología , Estrógenos no Esteroides/envenenamiento , Humanos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes/farmacología , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Células del Estroma/enzimología , Zeranol/envenenamientoAsunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Animales , Compuestos de Bencidrilo , Estrógenos no Esteroides/envenenamiento , Humanos , Síndromes de Neurotoxicidad/etiología , Fenoles/envenenamiento , Reproducción/efectos de los fármacos , RiesgoAsunto(s)
Consenso , Fenoles/envenenamiento , Efectos Tardíos de la Exposición Prenatal , Contaminantes Ocupacionales del Aire/envenenamiento , Animales , Animales Salvajes , Compuestos de Bencidrilo , Relación Dosis-Respuesta a Droga , Estrógenos no Esteroides/envenenamiento , Femenino , Humanos , Masculino , Modelos Animales , National Institutes of Health (U.S.) , North Carolina , Embarazo , Medición de Riesgo/métodos , Medición de Riesgo/normas , Estados Unidos , United States Environmental Protection AgencyRESUMEN
Man does not come into the world pre-determined. The lifetime set of environmental conditions impinging on a given individual has been termed the ambiome, which together with the genome and the proteome determines each individual's development and construction. Among the most important elements making up the ambiome are endocrine disruptors. An endocrine disruptor is a chemical substance that has adverse effects on an organism or its progeny, through the endocrine system. The number of known endocrine disruptors is large and continuously increasing, and includes both naturally occurring and synthetic substances. We are convinced that they entail genuine problems; although it is difficult to assess their magnitude and real significance, and we will certainly need some time, probably several decades, to obtain conclusive results; but even so, we consider that the existing body of evidence about effects of endocrine disruptors on human health is sufficiently worrying to justify precautionary measures.
Asunto(s)
Disruptores Endocrinos/envenenamiento , Enfermedades del Sistema Endocrino/inducido químicamente , Sistema Endocrino/efectos de los fármacos , Animales , DDT/envenenamiento , Dietilestilbestrol/envenenamiento , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Contaminantes Ambientales/envenenamiento , Estrógenos no Esteroides/envenenamiento , Femenino , Humanos , Masculino , Embarazo , Factores de Tiempo , Xenobióticos/envenenamientoRESUMEN
It has been shown that numerous natural and synthetic chemicals with estrogenic activities are reproductive or developmental toxic factors in humans or animals by epidemiological investigations and animal experiments. The mechanisms of toxicity, however, are very complicated, especially the molecular mechanisms. This article introduced the current progress on molecular mechanisms of toxicity, which included modulating signaling pathways, interfering gene expression during embryo stage, inducing mutation, etc.
Asunto(s)
Desarrollo Embrionario y Fetal/efectos de los fármacos , Estrógenos no Esteroides/envenenamiento , Isoflavonas , Fenoles/envenenamiento , Animales , Compuestos de Bencidrilo , Desarrollo Embrionario y Fetal/genética , Femenino , Humanos , Células Intersticiales del Testículo/efectos de los fármacos , Masculino , Fitoestrógenos , Preparaciones de Plantas , Embarazo , Efectos Tardíos de la Exposición PrenatalRESUMEN
Early embryonic and fetal development in mammals is sensitive to deficiencies and excesses of specific nutrients and toxicants. Operating directly and/or indirectly, these deficiencies and excesses can result in embryonic death or, in less severe circumstances, disruption of normal embryo and fetal growth. This paper explores the threats posed by feed and forage toxicants to the developing embryo and their impact on early programming of fetal development. Using significant examples, we consider the relevance of temporal sensitivities during early development in utero, and their implications for the morphology and functional competence of specific organs and tissues.