Early Mammalian Development: Nucleoside Transport and RNA Synthesis

Abstract

For studying early development, the mouse embro provides a convenient experimental model. Of particular interest is the transition from the cleavage (day 2) to the blastocyst (day 3) stage of development, a period of concurrent morphologic and molecular change. In addition to striking alterations in the activities of several enzymes, there is a marked change in the capacity of embryos incubated in vitro to take up uridine, a nucleoside precursor of RNA. The incorporation of 3H-uridine into the acid soluble pool follows Michaelis-Menten kinetics, and the maximal uptake (Vmax) is 8-fold greater in day 3 than in day 2 embryos. During the same time there is also an increase in the incorporation of 3H-uridine into embryos. During the same time there is also an increase in the incorporation of 3H-uridine into embryonic RNA. To distinguish a reak increase in RNA synthetic capacity from an apparent increase resulting from greater precursor uptake, embryos were incubated in the presence of varying concentrations of 3H-uridine. In day 3 embryos, saturation of the RNA synthetic system occurs prior to saturation of the transport system, and incorporation of uridine into RNA is independent of precursor concentration ≥ 1 μM. However, this is not the case in day 2 embryos: uridine incorporation into RNA parallels the uptake of uridine into the acid soluble pool. Therefore, it appears that the low rate of uridine incorporation into RNA by day 2 embryos is at least partially attributable to the low rate of precursor uptake. since preimplantation mouse embryos develop in vitro in the absence of uridine, the physiological role of the uridine transport system during this period is uncertain. Nonetheless, the preimplantation change in uridine transport is a striking developmental phenonmenon and may be important in preparing the embryo for the utilization of exogenous nutrients during postimplanatation growth and development.