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Master's Dissertation
DOI
10.11606/D.42.2016.tde-18042016-101410
Document
Author
Full name
Rafael Dalbosco dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Zorn, Telma Maria Tenorio (President)
Daher, Silvia
Ortis, Fernanda
Title in Portuguese
O impacto do diabetes Mellitus do tipo 1 sobre a ação da resposta proliferativa estimulada pela progesterona no ambiente uterino de camundongos.
Keywords in Portuguese
Diabetes
Estroma endometrial
Hoxa 10
p27
Progesterona
Receptor de progesterona
Abstract in Portuguese
A proliferação celular mediada pela progesterona (P4) é essencial para a funcão uterina. Dessa forma, alterações nesse processo podem comprometer a reprodução. O diabetes do tipo 1 (DM1) está associado a diversos distúrbios reprodutivos. No entanto, o impacto do DM1 sobre a ação da P4 no ambiente uterino ainda não é conhecido. Para isso, utilizamos fêmeas de camundongo DM1 induzidas por aloxana, submetidas à ovarectomia (OVX) e reposição por P4. Verificamos por meio de histomorfometria e imunohistoquímica (PCNA) uma diminuição da área de estroma uterino e do índice de proliferação. As quantificações proteícas por Western blot monstraram um aumento do PR-A nas fêmeas diabéticas OVX e nas tratadas pela P4. Ressalta-se que as fêmeas DM1 tratados pela P4 não apresentaram a mesma expressão do RNAm para o fator de crescimento Hoxa-10. Houve também um aumento do RNAm da p27 nas fêmeas DM1 não tratadas, visto por qPCR. Nossos resultados demonstraram que o DM1 interfere negativamente na resposta proliferativa promovida pela P4. Contribuindo para compreensão dos mecanismos biológicos pelos quais o diabetes compromete as funções reprodutivas.
Title in English
The impact of type 1 Diabetes Mellitus on the progesterone-mediated cell proliferative response on mice uterine environment.
Keywords in English
Diabetes
Endometrial stroma
Hoxa 10
p27
Progesterone
Progesterone receptor
Abstract in English
Progesterone (P4)-mediated cell proliferation is essential for uterine function. Therefore, alteration in this process could compromise reproduction. The type 1 diabetes (DM1) relates to several reproductive disturbs. However, the impact of DM1 on the P4 function is still not elucidated. Thus, we used alloxan-induced diabetic mice females subjected to ovariectomy and hormonal replacement therapy with P4. Histomorphometrical and immunohistochemistry to PCNA approaches showed a decrease of the uterine stromal area and the cell proliferation index. Protein quantification by Western blot showed increased levels of PR-A in both ovariectomized and P4-treated diabetic females. Importantly, P4 did not recovered the mRNA expression to the Hoxa-10 transcription factor in diabetic females. Additionally, qPCR analysis revealed increased level of p27 mRNA in diabetic females non-treated with P4. Together these results show that DM1 has a negative action on the P4-mediated cell proliferative response. These are new and important results to a better understand of the biological mechanisms by which diabetes affects the reproductive functions.
 
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Release Date
2018-04-18
Publishing Date
2016-04-18
 
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