Avaliação dos efeitos da exposição intrauterina ao 17ß-estradiol sobre o desenvolvimento prostático pós-natal no gerbilo da Mongólia

Author(s)

Bruno Domingos Azevedo Sanches

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2017-11-10

Examining board members

Sebastião Roberto Taboga; Murilo Vieira Geraldo; Daniela Carvalho dos Santos; Cristiane Damas Gil; Silvia Borges Pimentel de Oliveira

• Advisor: Sebastião Roberto Taboga

Abstract

Prostate development in rodent males has been extensively studied, which involves complex epithelial-mesenchymal interactions between the urogenital sinus epithelium (UGE) and the urogenital sinus mesenchyme (UGM). However, studies on the development of the prostate in females are scarce, such as hormonal manipulation studies on the development of the same. In parallel, prostatic stroma has been shown to be more complex at the cellular level, cells called telocytes have been recently described and supposed to exert several functions in the development and physiology of various organs, but there are no studies on the role of this cellular type in the prostate. The present study employed 3D reconstructions, histochemical, immunohistochemical and immunofluorescence techniques to describe comparatively the postnatal development among Mongolian gerbil males and females, as well as to evaluate the effects of intrauterine exposure to oestradiol on development and, finally, to investigate the presence of telocytes. We observed that the prostate of the females has its branching and differentiation process induced by a single mesenchyme, which presents a ventrolateral disposition, which we denominate Ventrolateral Mesenchyme (VLM), in addition, the female prostate shows an earlier pre-maturation than that of male, which could be justified by the higher estrogen sensitivity and the reduction in ERalpha expression along with the earlier expression of epithelial AR. The prostate of the females was also more sensitive to intrauterine exposure to 17beta-estradiol, it was verified a reduction in the number of prostatic branches and morphological changes due to a low dose exposure of this hormone (500ng.BW/D). In addition, our data point to the occurrence of prostate telocytes closely associated with the periductal smooth muscle, which could indicate a possible role in the differentiation process of this muscle and, later, these cells are verified in the interalveolar region and between the prostatic stroma and the periuretral smooth muscle, which may indicate a role of telocytes in the prostatic tissue organization. Finally, c-Kit positive Interstitial Cajal-like cells (ICLCs) were detected in the stroma and we found evidences that telocytes could be progenitor cells of these. In general terms, our data point to a greater sensitivity of the female prostate to the E2, which becomes worrisome due to the presence of prostate in a portion of the women, moreover, our findings indicate a greater complexity of the prostate stroma at the cellular level, evidenced by the presence of telocytes and c-Kit positive ICLCs (AU)

• FAPESP's process: 13/15939-0 - Evaluation of intrauterine oestrogenic exposure on the main epithelium-mesenchyme interaction pathways in the branching morphogenesis in the Mongolian Gerbil prostrate ventral lobe
• Grantee: Bruno Domingos Azevedo Sanches
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)