Effect of glucose-6-phosphate dehydrogenase inhibition on trophectoderm differentiation in bovine embryos

• Grant number: 24/10421-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Marcelo Demarchi Goissis
• Grantee: Julia Gil Velho Rocha
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/06051-8 - Effects of metabolic modulations on the initial cell differentiation of bovine embryos, AP.R

Abstract

The trophectoderm (TE) has the role to form the placenta, and the primary events of cellular differentiation lead to its formation. During the process of TE specification, the inhibition of enzymes that push glucose incorporation into metabolic pathways, such as the pentose phosphate pathway (PPP), led to a block in the formation of this cell layer in mice. Inhibition of glucose-6-phosphate dehydrogenase (G6PD) can result in a negative response of transcription factors related to TE formation. It is expected that inhibition of G6PD will also inhibit the PPP pathway, thereby decreasing NADPH within the cell. Thus, the current project aims to test the hypothesis that the PPP plays an important role on the TE formation in cattle, considering that studies regarding this species are scarcer compared to what is known about mice. The goal is to pharmacologically inhibit G6PD and assess the gene expression of transcription factors related to the TE at the morula stage and quantitate TE cells in blastocysts by immunofluorescence. Ultimately, this project aims to understand an aspect of cellular differentiation of in-vitro produced bovine embryos, with the potential to modulate the allocation of trophectoderm cells.