Compensatory Mechanisms In Mouse Offspring With Inherently Weak Bones Are Suggesting A Gene-By-Environment Interaction In Utero

Exposure of mouse embryo to different environmental factors, including sub-threshold teratogens, can detrimentally affect bones of the offspring later in life. We investigated to what extent the genetic differences translate into variable response to teratogen 5-deoxy-2'-cytidine (5-AZA). We used mice of 2 inbred strains, C3H/HeJ (with inherently stronger bones) and C57Bl/6J (with weaker bones). Mothers were injected with 5-AZA or saline (control) at day 10 of pregnancy. Five offspring of mice from each strain/sex groups (C3H or C57, males and females), treated and untreated, were tested at age 3 mo (adolescent) and 6 mo (adult). Femora from 80 offspring were analyzed by Scanco μCT50. At the age of 3-mo, treated females (C57) had significant decrease (p<0.05) of bone mineral density (BMD) or loss of trabecular thickness (C3H); treated mice demonstrated loss of cortical thickness (p<0.05). In 6-mo-old, BMD was slightly lower in treated C3H males and females, while treated C57 had increased trabecular thick...