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Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats
Emmanuel Somm1, Delphine M Vauthay, Audrey Guérardel
1Department of Paediatrics, University of Geneva School of Medicine, Geneva, Switzerland. emmanuel.somm@unige.ch
Insights
Poor fetal growth (IUGR) in rats, caused by dexamethasone or undernutrition, leads to early metabolic issues like high blood sugar and pancreatic damage, impacting long-term health.
Area of Science:
- Endocrinology
- Developmental Biology
- Metabolic Syndrome Research
Background:
- Poor fetal growth, or intrauterine growth restriction (IUGR), is a global health issue linked to perinatal mortality and later chronic metabolic diseases.
- IUGR can cause "metabolic programming," increasing risks for obesity, type 2 diabetes, and metabolic syndrome.
- Understanding early IUGR-induced alterations is crucial for preventing long-term health consequences.
Purpose of the Study:
- To investigate early physiological, morphometric, and transcriptomic changes in IUGR rat models.
- To analyze the impact of prenatal dexamethasone (DEX) exposure and prenatal undernutrition (UN) on IUGR development.
- To focus on the endocrine pancreas and adipose tissue during early life stages.
Main Methods:
- Two IUGR rat models were established: prenatal dexamethasone exposure (DEX) and prenatal undernutrition (UN).
- Physiological assessments included glucose and insulin tolerance tests.
- Morphometric analysis used automated tissue image analysis, and transcriptomic analysis employed quantitative PCR.
Main Results:
- Both DEX and UN IUGR pups exhibited basal hyperglycemia, decreased glucose tolerance, and pancreatic islet atrophy before catch-up growth.
- DEX-exposed pups showed reduced insulin sensitivity.
- UN-exposed pups displayed impaired glucose-induced insulin secretion and significant gene expression alterations in pancreatic and adipose tissues.
Conclusions:
- IUGR, induced by prenatal DEX or UN, results in early physiological, morphological, and transcriptomic defects in rat pups.
- These early defects precede catch-up growth and represent the initial mechanistic basis for metabolic programming.
- The findings highlight critical developmental windows for intervention to mitigate long-term metabolic risks associated with IUGR.
Abstract:
Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.
