The transgenerational effect of maternal and paternal F1 low birth weight on bone health of second and third generation offspring

Abstract

AbstractLow birth weight programs diseases in adulthood, including adverse bone health. These diseases can have intergenerational and transgenerational origins, whereby transmission to subsequent generations occurs via both parental lines. Uteroplacental insufficiency surgery (Restricted) or sham surgery (Control) was performed on gestational day 18, in F0 Wistar–Kyoto rats. F1 Restricted males and females mated with breeders in order to generate F2 offspring of maternal and paternal lineages. F2 males and females were randomly selected for breeding to generate F3 offspring. F2 and F3 offspring did not have differences in birth weight irrespective of F1 low birth weight and parental line. Maternal line females had minor alterations to trabecular content and density at 6 months, these differences were not sustained at 12 months. Maternal line males had changes to trabecular content at 6 and 12 months; however, differences were no longer present at 16 months. Despite altered bone geometry at 12 and 16 months, bending strength remained unaffected at both ages. Bone health of paternal line females was not affected at 6 and 12 months. Paternal line males at 6 months had changes to trabecular and cortical content; cortical thickness, periosteal circumference and bending strength; however, these differences were no longer sustained at 12 and 16 months. Our data demonstrate that there is no transgenerational transmission of adverse bone health in F2 and F3 offspring, derived from low F1 birth weight females and males. Our results are novel, as bone health across generations and both parental lines has not been investigated in a model of low birth weight due to uteroplacental insufficiency.