Culture of preimplantation mouse embryos affects fetal development and theexpression of imprinted genes

Culture of preimplantation mammalian embryos and cells can influence their subsequent growth and differentiation. Previously, we reported that culture of mouse embryonic stem cells is associated with deregulation of genomic i mprinting and affects the potential for these cells to develop into normal fetuses. The purpose of our current study was to determine whether culture of preimplantation mouse embryos in a chemically defined medium (M16) with or without fetal calf serum (FCS) can affect their subsequent development a nd imprinted gene expression. Only one third of the blastocysts that had be en cultured from two-cell embryos in M16 medium complemented with FCS devel oped into viable Day 14 fetuses after transfer into recipients, These M16 FCS fetuses were reduced in weight as compared with controls and M16 fetus es and had decreased expression of the imprinted H19 and insulin-like growt h factor 2 genes associated with a gain of DNA methylation at an imprinting control region upstream of H19. They also displayed increased expression o f the imprinted gene Grb10. The growth factor receptor binding gene Grb7, i n contrast, was strongly reduced in its expression in most of the M16 + FCS fetuses. No alterations were detected for the imprinted gene Mest. Preimpl antation culture in the presence of serum can influence the regulation of m ultiple growth-related imprinted genes, thus leading to aberrant fetal grow th and development.