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Papel del receptor de estrógenos β en los efectos de la exposición prenatal al bisfenol-a en la célula β pancreática


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Título :
Papel del receptor de estrógenos β en los efectos de la exposición prenatal al bisfenol-a en la célula β pancreática
Autor :
Boronat-Belda, Talía  
Tutor:
Nadal, Angel  
ALONSO MAGDALENA, PALOMA  
Editor :
Universidad Miguel Hernández de Elche
Departamento:
Departamentos de la UMH::Fisiología
Fecha de publicación:
2021-04-13
URI :
https://hdl.handle.net/11000/28945
Resumen :
La exposición al disruptor endocrino BPA, durante la gestación, conduce a alteraciones metabólicas en la descendencia produciendo efectos adversos en la homeostasis de glucosa y, por tanto, a un aumento del riesgo en la aparición de enfermedades metabólicas como la diabetes mellitus tipo 2. Por otr...  Ver más
Gestational exposure to BPA leads to metabolic disorders in the offspring which may increase the risk of developing diseases like type 2 diabetes. BPA is also known to activate different signalling pathways through activation of estrogen receptors (ERs) which may alter gene expression and pancreatic β-cell function. In the present work, we analyse the effects of gestational exposure to BPA on pancreatic β-cell function and mass in the offspring during first month of life as well as the role of ERs. We use OF1 mice to investigate the effects of BPA on pancreas development in the offspring exposed. To uncover the possible participation of ERβ animals from BERKO colony were included in the study. Pancreatic β-cell mass and proliferation was analysed in the offspring at postnatal day 0 (P0) and 30 (P30) by means of histological and morphometric procedures. Pancreatic β-cell function was explored at P30. Glucose tolerance, insulin sensitivity, in vivo and ex vivo insulin secretion response, changes on gene expression as well plasma levels of hormones key in glucose and energy homeostasis were analysed. In addition to that, in order to explore ERβ role in the proliferative effect of BPA in pancreatic β-cells, a series of in vitro experiments were performed. Dispersed pancreatic islet cells from adult male WT and BERKO mice were cultured in the presence of vehicle or BPA, a specific agonist of ERβ, WAY200070, a specific agonist of ERα, PPT, or the natural hormone 17β-estradiol. We found that gestational exposure to BPA led to a significant increase of pancreatic β-cell area and mass in the OF1 male offspring. This increment was related to enhanced pancreatic β-cell proliferation rate and decreased apoptosis. Similar results were observed in WT exposed animals from the BERKO colony while mice lacking ERβ did not show any change. In vitro experiments revealed that BPA, at environmentally relevant doses, promoted increased pancreatic β- cell division in an ERβ-dependent manner. Nevertheless, we cannot discard that other ERs like ERα may also play a role since the treatment with the selective agonist of ERα, PPT, also increased β-cell replication rate. On the contrary, the treatment with 17β-estradiol, in the same range of doses, did not promote any change on β-cell proliferation neither in males nor in females WT. As regards the in vivo study of glucose homeostasis, no significant effects were observed on glucose tolerance, insulin sensitivity or plasma hormone levels in the male offspring in utero exposed to BPA at P30. However, we do observe that BERKO animals showed decreased insulin secretion in response to stimulatory glucose concentrations. In summary, in the present study we demonstrate that in utero exposure to BPA promote early changes in the morphology of the endocrine pancreas in an ERβ- dependent manner. In addition, we found that BPA, at doses within the range of human exposure, modulates pancreatic β-cell division leading to an increment of pancreatic β-cell mass during development. This finding will contribute to expand our knowledge on the mechanisms underlying BPA action which may have an impact on glucose homeostasis.
Palabras clave/Materias:
Fisiología endocrina
Área de conocimiento :
CDU: Ciencias aplicadas: Medicina: Fisiología
Tipo de documento :
info:eu-repo/semantics/doctoralThesis
Derechos de acceso:
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Aparece en las colecciones:
Tesis doctorales - Ciencias e Ingenierías



Creative Commons La licencia se describe como: Atribución-NonComercial-NoDerivada 4.0 Internacional.