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Glucocorticoids impair fetal beta-cell development in rats
B Blondeau1, J Lesage, P Czernichow
1Institut National de la Santé et de la Recherche Médicale Unité 457, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France.
American Journal of Physiology. Endocrinology and Metabolism
|August 14, 2001
Summary
Maternal undernutrition and glucocorticoid overexposure during pregnancy negatively impact fetal beta-cell development. Reducing corticosterone levels in fetuses improved beta-cell mass, suggesting a key role for glucocorticoids.
Area of Science:
- Endocrinology
- Developmental Biology
- Metabolic Research
Background:
- Maternal undernutrition and in utero glucocorticoid overexposure are linked to fetal growth retardation and later glucose intolerance.
- Glucocorticoids are implicated in intrauterine growth retardation and subsequent metabolic dysfunction in rodents.
Purpose of the Study:
- To investigate if glucocorticoid overexposure mediates the effects of maternal undernutrition on fetal beta-cell mass.
- To examine the role of glucocorticoids in fetal beta-cell development in normally nourished rats.
Main Methods:
- Rats were subjected to maternal food restriction or normal nutrition during pregnancy.
- Maternal and fetal corticosterone levels were measured.
- Surgical interventions (adrenalectomy) and pharmacological treatments (metyrapone) were used to manipulate corticosterone levels.
- Fetal pancreatic insulin content and beta-cell mass were assessed.
Main Results:
- Undernutrition increased maternal and fetal corticosterone, leading to fetal growth retardation and decreased pancreatic insulin content.
- Maternal adrenalectomy or corticosterone implants normalized fetal beta-cell mass in undernourished fetuses.
- In normally nourished fetuses, higher corticosterone levels correlated negatively with fetal weight and insulin content.
- Inhibition of steroidogenesis in normally nourished fetuses significantly increased fetal beta-cell mass.
Conclusions:
- Glucocorticoids play a negative role in fetal beta-cell development.
- Maternal undernutrition-induced reduction in beta-cell mass may be mediated by increased fetal corticosterone exposure.
- Modulating glucocorticoid levels during gestation could be a therapeutic target for preventing fetal growth restriction-associated metabolic disorders.