Calendário de Defesas e Seminários

JOÃO MATHEUS BREMM - PPGBM
Defesa de Dissertação - Mestrado
 
Data: Quarta-feira, 22 de Maio de 2019 (12:00 - 23:59)
 

Investigating the role of EGF-CFC gene family in recurrent pregancy losses through multiple approaches

Orientadora: Dra. Maria Teresa Vieira Sanseverino

Coorientador: Dr. Lucas Rosa Fraga

Avaliador: Dr. Juliano André Boquett

Abstract:

Recurrent pregnancy loss (RPL) is one of the most frequent reproductive failures, affecting 1-5% of women throughout their lives, and its etiology remains unknown in around 50% of cases. EGF-CFC gene family composed, in humans, of the genes Cripto-1 (TDGF1) and Cryptic (CFC1), both important for embryonic development, angiogenesis and the establishment of body axes. The objective of this study was to evaluate the role of these genes in RPL. For this, multiple approaches were carried out: in silicoanalyses through functional predictions and systems biology; molecular analyzes through a case-control study; and expression analyzes using secondary data from the Gene Onibus Expression (GEO) database. First, we performed a scan of the polymorphic variants of each of these genes using theEnsembl database, and score of pathogenicity score for these variants was developed. We found as the most relevant variants, the rs3806702 (c-14 + 1429T> C) in Crypto-1 (TDGF1) and rs201431919 (p.Arg47Gln) in Cryptic (CFC1). We then evaluated the frequencies of these variants in a sample of 149 women with RPL and 159 controls (having at least two successful pregnancies and no history of pregnancy loss). We did not find differences in allelic and genotypic frequencies between these two groups. Next, we performed expression analyzes with secondary datastored in GEO, which showed a decrease in the expression of Crypto-1 (TDGF1) gene in the endometrium of women with RPL (p = 0.049) and Cryptic (CFC1) in placenta of women with RPL (p = 0.015) suggesting a possible influence of the EGF-CFC family on RPL. Finally, network and ontology analysis and literature review pointed to a strong relationship among EGF-CFC family and cellular responses involving the TGF-β, AKT, MPK, SRC, Wnt, Notch, TNFα, IFNγ, IL -6 and FGF signaling pathways. These pathways play key roles during pregnancy by controlling inflammatory response, cell proliferation, decidualization, angiogenesis, apoptosis, embryo-maternal recognition, embryo implantation, placentation as well as embryonic development. Although we are not able to point out the exact molecular mechanisms of which this family is involved to RPL, the results here presented indicate the involvement of Crypto-1 andCrypticin this condition. Therefore, more studies on this gene family and related genes are necessary to elucidate the precise mechanisms that influence the etiology of RPL.

 

 

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por Tamara Moch