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Effects of hormones and citokynes in the indoleamine 2,3-dioxygenase expression and the proliferative capacity of cells from bovine placenta

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Author(s):
Ana Rita de Lima
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
Defense date:
Examining board members:
José Roberto Kfoury Junior; Durvanei Augusto Maria; Maria Angélica Miglino; Paula de Carvalho Papa; Flávia Thomaz Veréchia Pereira
Advisor: José Roberto Kfoury Junior
Abstract

Indoleamina 2,3-dioxigenase (IDO) is an enzyme that plays an important role in preventing fetal rejection. IDO is related to the suppression of the T-cells activation due to the catabolism of essential amino acid Triptophan. We studied the expression of IDO in bovine placenta cell culture with individual supplementation of factors as Estrogen, Progesterone, Interferon , Triptophan and 1-Methyl-Triptophan. Evaluations were made by flow cytometry, immunocitochemistry and cellular quantification, lipidic peroxidation, cell cycle phases, imunoblotting, PCR and immunofluorescency in the three trimesters of pregnancy. Cellular quantification demonstrated that in bovines the activity of the IDO increases during pregnancy, and its expression is factor-dependent, which was also observed in immunofluorescency. Imunoblotting demonstrated the presence of possible unknown protein isoforms in bovine. Lipoperoxidation evaluation demonstrated that hormones distinguishingly modulated the production of peroxide radicals in the three trimesters of pregnancy and, possibly acting as inductive factors of proliferation. Placental cells demonstrated differentiated patterns of proliferation and apoptosis during the gestation, mainly in the presence of Estrogen and Progesterone, besides variant rates were also observed under other factors. Independent of the concentration, Progesterone influenced placental cells maturation. All groups presented great ratio of cells in quiescence state (G1). In third trimester, G2/M high rates indicated a pause in proliferative capacity or in cell cycle progression (arrest). High apoptosis rates were observed in animals at second pregnancy trimester. Based on the presented, we concluded that IDO is susceptible to be controlled by the applied-factors, what lead us to think about hypothetical therapeuthic mechnism for reproduction with the participation of IDO. (AU)