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Effect of inhibition of fibroblast growth factor receptors in the differentiation of primitive endoderm in bovine embryos produced in vitro

Grant number: 19/21303-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): July 13, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Reproduction
Principal Investigator:Marcelo Demarchi Goissis
Grantee:Gabriel Siqueira dos Santos
Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:17/09576-3 - Studies on cell differentiation mechanisms during early bovine embryo development, AP.JP


Segregation of cell lines and implantation of the embryo are definitive events for successful gestation. The first cell divisions results in the division between trophectoderm (TE) and inner cell mass (ICM). Following, ICM is then differentiated into epiblast (EPI) and primitive endoderm (PE). It is known that in murine embryos transcription factor NANOG promotes secretion of fibroblastic growth factor (FGF) which actives FGF receptors (FGFR), and subsequently actives MEK/ERK pathway. This mecanism leads to differentiation of MCI cells in PE cells. Recent studies suggest that MEK/ERK inhibition pathway reduces the number of PE cells in bovine embryos. This study hypotesis is that signaling by FGF receptors does not interfere in PE specification in bovine embryos. The aim of this study is to evaluate the role of FGF signalling in EPI and PE specification in bovine embryos by pharmacological inhibition of FGFR. Bovine in vitro produced embryos will be pharmacological treated with the inhibitor FGFR AZD4547 in different embryo development times: day 5 to day 7 after in vitro fertilization, day 7 to day 9, the third from day 5 to day 9. Also will be a control group non-treated, and another one group treated with DMSO. Blastocists will be fixed in paraformaldehyde to immunofluorescense, aiming at verify cells that express GATA6, NANOG and SOX17 by confocal microscopy. With the results of this studt, it is expected understand better the role of signaling of FGF in EPI and PE segregation.

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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)
SANTOS, GABRIEL S.; MARTINS, MATHEUS P.; LUEDKE, FELIPE E.; TANAKA, YUKI; CARREIRO, LETICIA E.; MENDES, CAMILLA MOTA; GOISSIS, MARCELO DEMARCHI. Inhibition of FGF receptor impairs primitive endoderm differentiation in bovine embryos. REPRODUCTION IN DOMESTIC ANIMALS, v. 58, n. 2, p. 9-pg., . (19/21303-8, 19/22798-0, 17/09576-3)
CARREIRO, LETICIA ESCOBAR; DOS SANTOS, GABRIEL SIQUEIRA; LUEDKE, FELIPE EDUARDO; GOISSIS, MARCELO DEMARCHI. ell differentiation events in pre-implantation mouse and bovine embryo. ANIMAL REPRODUCTION, v. 18, n. 4, . (19/22649-5, 19/21303-8, 19/03014-9, 17/09576-3)
LETÍCIA ESCOBAR CARREIRO; GABRIEL SIQUEIRA DOS SANTOS; FELIPE EDUARDO LUEDKE; MARCELO DEMARCHI GOISSIS. Cell differentiation events in pre-implantation mouse and bovine embryos. Animal Reproduction, v. 18, n. 4, . (19/22649-5, 19/21303-8, 19/03014-9, 17/09576-3)

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