, Volume 45, Issue 3, pp 394-401
Date: 05 Apr 2014

Endocrine pancreas development is altered in foetuses from rats previously showing intra-uterine growth retardation in response to malnutrition

Abstract.

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]

Received: 16 July 2001 and in revised form: 17 October 2001