GM-CSF perturbs cell identity in mouse pre-implantation embryos

Area of Science:

• Developmental Biology
• Reproductive Medicine
• Cell Biology

Background:

• Growth factors are explored for improving embryo culture media to better mimic in vivo conditions.
• Granulocyte macrophage colony-stimulating factor (GM-CSF), a cytokine, influences the maternal-fetal interface and placental development.
• GM-CSF is clinically used, with trials suggesting improved embryo survival, particularly in women with recurrent miscarriages.

Purpose of the Study:

• To investigate the impact of GM-CSF supplementation on cell number and lineages in early pre-implantation mouse embryos.
• To compare the effects of mouse GM-CSF versus human GM-CSF (hGM-CSF) in different culture media.
• To assess potential changes in cell identity, including NANOG expression, within the developing embryo.

Main Methods:

• Culture of early pre-implantation mouse embryos in standard human ART media and optimized mouse media.
• Supplementation of media with varying concentrations of mouse GM-CSF or hGM-CSF.
• Analysis of total cell number, cell lineage distribution (TE, primitive endoderm, epiblast), and NANOG expression.

Main Results:

• Mouse GM-CSF significantly increased total cell numbers in a dose-dependent manner.
• This increase was attributed to changes in trophectoderm (TE) and primitive endoderm cell numbers, not epiblast.
• Ectopic NANOG expression was observed in TE cells across various media conditions, notably increasing with GM-CSF concentrations.

Conclusions:

• GM-CSF influences cell number and identity in mouse pre-implantation embryos, specifically affecting TE and primitive endoderm development.
• The observed ectopic NANOG expression in TE cells raises concerns about potential impacts on embryo development and post-implantation phases.
• Caution is advised regarding the use of unresearched supplements in embryo culture due to potential risks.