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Evaluation of the effects of finasteride on intrauterine and early post-natal prostatic development of Mongolian Gerbil (Meriones unguiculatus)

Grant number: 16/16509-8
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2016
Effective date (End): October 31, 2018
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Sebastião Roberto Taboga
Grantee:Juliana dos Santos Maldarine
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The prostate is a reproductive accessory gland present in mammals, and the study of its formation is relevant for investigation of the correlation between the development and tumorigenesis, especially in the study of susceptibility to tumorigenesis and other pathological conditions due to hormonal manipulation. The formation of prostate initially involves epithelial-mesenchymal interactions between outgrowths of the epithelium of the urogenital sinus (UGE) and the urogenital sinus mesenchyme (UGM), constituting the budding stage of the gland. Later, these buds reach peripheral mesenchymes to UGM, which the most investigated is the Ventral mesenchymal pad (VMP), and branch, forming the gland branching phase, and, finally, these branches suffer canalization and give rise to the secretory portion of the gland, the prostatic acini, and the conducting portion of the gland, the prostatic ducts. Meanwhile, the peripheral mesenchymes give rise to prostatic stroma, this final step constitutes the process of morphofunctional differentiation of the gland. The Mongolian gerbil (Meriones unguiculatus) is promising for research on prostate development, since the prostate is present in about 90% of females, unlike other laboratory rodents, such as rats and mice that lack functional prostate in females. Much has been investigated about the prostate gland in females, but the reason for the occurrence of prostate in a proportion of females remains unclear, as about the role of testosterone on the initial development of female prostate and about the origin of susceptibility differences to pathological conditions in the prostate between the sexes. This project uses finasteride, an inhibitor of 5-±-reductase, the enzyme that converts testosterone in its most active form: dihydrotestosterone, to evaluate the effects of the reduction of androgen action on the prostate at two different moments of its development: First in the intrauterine period in order to assess whether a critical dose of testosterone is required for the development of prostate in females, and in a second stage on the post-natal period, more specifically during the branching phase, so to assess the disruptive effect of reduced androgenic activity on the prostate especially on the major paracrine pathways involved in prostate development. For this study will be used immunohistochemical techniques, three-dimensional reconstructions and serum hormone levels analysis. This study is particularly relevant in view of the sensitivity of the prostate to hormone fluctuations, and lack of studies on hormone dynamics that leads to the female prostate development and alterations that this may undergo in its initial development, which is important in face of the presence of a functional prostate in one third to half of the women, issue that remain poorly studied, as well as with the occurrence of tumors of prostatic origin in women.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MALDARINE, JULIANA S.; SANCHES, BRUNO D. A.; SANTOS, VITORIA A.; AMARO, GUSTAVO M.; CALMON, MARILIA F.; RAHAL, PAULA; GOES, REJANE M.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R. Low-dose in utero exposure to finasteride promotes developmental changes in both male and female gerbil prostates. ENVIRONMENTAL TOXICOLOGY, AUG 2019. Web of Science Citations: 0.

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