Developmental effects following irradiation of early mammalian embryos

NOTE: Developmental effects following irradiation of early mammalian embryos with moderate doses of x-rays : transmission to the following generation (FP6 Euratom contract, 2006-2010)

In man, it is virtually impossible to investigate events occurring in the embryo before its implantation into the uterus, since conception is generally not noticed at that early period of pregnancy. Therefore, risk analysis for the preimplantation period and the very early postimplantation period (first week of development in humans and other mammalian species) can only be achieved on the basis of animal experiments.

Until recently, it was assumed that irradiation of preimplantation embryos can only result into the early death and elimination of the embryo or its survival without anomaly. This was the so-called “all-or-none” rule. However, we and others showed that at least in some “sensitive” mouse strains, X-irradiation at these early stages could also result into more or less severe congenital anomalies in the surviving embryos. Highest rates of congenital anomalies were found when irradiation occurred at the one-cell stage (first 24 h of development).

The aim of our present studies is to determine whether developmental defects are still observed in the next generation following radiation exposure of preimplantation embryos, as well as to shed light on the mechanisms involved in those effects. For this purpose, one-cell embryos from two radiation sensitive strains (CF1 and ICR) are x-irradiated in vivo with moderate doses of x-rays (0.2 or 0.4 Gy). After birth, normal appearing female progeny is allowed to reach sexual maturity, then mated with control males.

Analysis of the transmitted radiation effects is performed at the levels of embryonic/foetal death, growth retardation and congenital anomalies. With regard to the mechanisms potentially involved, particular attention is paid to the secretion of specific proteins like pro-inflammatory cytokines in the amniotic fluid surrounding the foetuses, the radiation induction of a genomic instability as well as of changes in the profiles of gene expression in the embryonic tissues.

People: Dr. Paul Jacquet , Dr. S. Baatout, Dr. R. Benotmane, Dr. H. Derradji, J. Buset, L. Leyns, A. MichauxM. Neefs