Control of trophectoderm differentiation by inner cell mass-derived fibroblast growth factor-4 in mouse blastocysts and corrective effect of FGF-4 onhigh glucose-induced trophoblast disruption

Previous studies have suggested that fibroblast growth factor-4 (FGF-4) may be a paracrine signal used by inner cell mass (ICM) cells to maintain adja cent trophectoderm (TE) cells in an undifferentiated state. In the present work, immunocytochemical analysis of mouse blastocysts confirmed that FGF-4 was predominantly detected in the ICM before and after spreading over a fi bronectin-coated culture substrate. Addition of human recombinant FGF-4 did not influence morphological progression, cell allocation and proliferation in ICM and TE lineages or mitosis and karyorhexis frequencies during blast ocyst expansion. Addition of FGF-4 to outgrowing blastocysts, in contrast, induced a significant decrease in the surface of the trophoblast outgrowths formed by the TE cells and in the proportion of giant trophoblasts per out growth. The fact that blastocysts display excessive trophoblast expansion a nd spreading over their culture substrate upon pre-exposure to high concent rations of glucose in vitro was used to further assess the regulatory effec t of FGF-4. Addition of FGF-4 was indeed found to fully neutralize the disr uptive impact of high glucose on trophoblast outgrowths. Altogether, our da ta indicate that ICM-derived FGF-4 participates actively in the regulation of trophoblast development.