Aims/hypothesis:  

We have shown that perinatal malnutrition decreases beta-cell mass at birth and impairs the adaptation of the endocrine pancreas to a subsequent pregnancy. The aim of this study is to investigate the impact of this maternal inadaptation on the development of endocrine pancreas in foetuses.

Methods:  

Female rats malnourished during their perinatal life and showing intra-uterine growth retardation at birth were mated at 8 months of age. The development of the endocrine pancreas was studied at embryonic days 14, 17 and 20 in their foetuses by immunohistochemistry and morphometrical measurements on pancreatic sections.

Results:  

At embryonic day 20, both alpha and beta-cell fractions were decreased in foetuses from IUGR dams. Beta-cell mass was reduced (197 ± 27 μg, vs 281 ± 40 μg in control, p < 0.01) and so were insulin content and islet number per cm², as in the first generation foetuses. At embryonic day 14, the number of cells expressing only insulin was decreased by half in foetuses from intra-uterine growth retardation dams. At embryonic day 17, 50 % of the homeodomain protein Pdx-1 cell population expressed insulin but all the insulin cells expressed Pdx-1 in both groups; in foetuses from intra-uterine growth retardation dams the number of epithelial cells expressing Pdx-1 was decreased (415 ± 40 cells/ mm² vs 481 ± 28 cells/mm² in control foetuses, p < 0.05) and the mesenchymal fraction in the pancreas was increased by 36 % (p < 0.05).

Conclusion/interpretation:  

Early malnutrition decreases beta-cell mass in the first generation of offspring and impairs the subsequent beta-cell adaptation to pregnancy. The beta-cell alteration is also present in the next generation and involves a decreased expansion of the epithelial population expressing Pdx-1. [Diabetologia (2002) 45: 394–401]