Maternal obesity affects gene expression and cellular development in fetal brains

Abstract

Objectives

Female rat neonates reared on a high carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Furthermore, we have shown that fetal development in the HC intrauterine environment (maternal obesity complicated with hyperinsulinemia, hyperleptinemia, and increased levels of proinflammatory markers) resulted in increased levels of serum insulin and leptin in term HC fetuses and the spontaneous transfer of the HC phenotype to the adult offspring. The objectives of this study are to identify changes in global gene expression pattern and cellular development in term HC fetal brains in response to growth in the adverse intrauterine environment of the obese HC female rat.

Methods

GeneChip analysis was performed on total RNA obtained from fetal brains for global gene expression studies and immunohistochemical analysis was performed on fetal brain slices for investigation of cellular development in term HC fetal brains.

Results

Gene expression profiling identified changes in several clusters of genes that could contribute to the transfer of the maternal phenotype (chronic hyperinsulinemia and adult-onset obesity) to the HC offspring. Immunohistochemical analysis indicated diminished proliferation and neuronal maturation of stem-like cells lining the third ventricle, hypothalamic region, and the cerebral cortex in HC fetal brains.

Discussion

These results suggest that maternal obesity during pregnancy could alter the developmental program of specific fetal brain cell-networks. These defects could underlie pathologies such as metabolic syndrome and possibly some neurological disorders in the offspring at a later age.

Keywords:

• Fetal hyperinsulinemia and hyperleptinemia
• Global gene expression
• Maternal obesity
• Neurogenesis
• Neuronal maturation

Acknowledgement

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-61518 (MSP). We thank Dr Luidmila Pliss for performing the perfusion of the fetuses.