Endocrine Abstracts

Maternal undernutrition has been demonstrated to impact upon the development of a number of organ systems, including the kidney and pancreas. Offspring exposed to a maternal dietary protein restriction during gestation exhibit livers with fewer, larger lobules, suggestive of a similar developmental defect. It has been previously suggested that developmental changes, at least in the kidney, might be mediated by a change in the expression of the transcription factor Prox1. Here, we set out to establish whether liver development in the mid-gestation mouse is influenced by maternal undernutrition and whether this coincides with changes in Prox1 expression. Female mice were supplied either an 18% protein diet (CTRL) or a 9% protein diet (MLP) from conception and sacrificed at embryonic day 14. Fetal livers were removed and processed for cryosectioning. Liver weight at this time-point was not influenced by maternal diet (CTRL – 21±1 mg, MLP – 26±2 mg; P=0.110). Exhaustive immunohistochemical analysis of Prox1 positive nuclei showed numerical differences between CTRL (6.5±2.7 cells/unit area) and MLP (13.8±2.5 cells/unit area) livers, but this did not reach statistical significance, suggesting that the expression of Prox1 is not influenced by maternal diet in liver tissue at this developmental stage (P=0.120). However, examination of cell populations (as defined by their size and structure) revealed a considerably elevated density (3 fold higher – P<0.01) of undifferentiated hepatoblasts in MLP animals compared with controls. Our data suggest that maternal undernutrition impacts upon liver development in mid-gestation by impeding hepatoblast differentiation, but that this may not be mediated by changes in Prox1 expression. Future work will be directed towards understanding the mechanisms by which maternal dietary protein restriction might impede differentiation of hepatocyte progenitors and whether this is a determining factor in altering structure and postnatal function.