Related Experiment Video
Updated: Mar 14, 2026
Derivation of Glial Restricted Precursors from E13 mice
Published on: June 20, 2012
Transcriptomic regulations in oligodendroglial and microglial cells related to brain damage following fetal growth
Aline Rideau Batista Novais1,2,3,4, Hoa Pham1,4, Yohan Van de Looij5,6
1Institut National de la Santé et de la Recherche Médicale (Inserm) U1141, Paris, France.
Insights
Fetal growth restriction (FGR) in rats impairs brain development, causing white matter issues and reduced connectivity. This study suggests neuroinflammation underlies poor neurocognitive outcomes in growth-restricted infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Fetal growth restriction (FGR) is a pregnancy complication linked to neurocognitive deficits.
- Mechanisms connecting FGR to impaired brain development remain unclear.
Purpose of the Study:
- To investigate the relationship between FGR, gene expression changes, and brain abnormalities in a rat model.
- To correlate FGR-induced gene expression alterations with white matter maturation, brain microstructure, and cortical connectivity.
Main Methods:
- Utilized a rat model of FGR induced by maternal low-protein diet.
- Employed advanced brain imaging (MRI, ultrafast ultrasound), microarray analysis of glial cells, and histology.
Main Results:
- FGR significantly altered myelination and brain function, with white matter changes detected early via MRI.
- Reduced cortical connectivity was observed, alongside evidence of white matter dysmaturation.
- Transcriptomic analysis revealed myelination deficits and deregulation of neuroinflammation and cell cycle genes in oligodendrocytes and microglia.
Conclusions:
- FGR leads to significant white matter abnormalities and impaired brain function in rats.
- Neuroinflammation and cell cycle dysregulation in glial cells are key mechanisms in FGR-induced brain defects.
- Findings suggest a neuroinflammatory basis for neurocognitive impairments in human infants with FGR.
Abstract:
Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology. We show that myelination and brain function are both significantly altered in our model of FGR. These alterations, detected first in the white matter on magnetic resonance imaging significantly reduced cortical connectivity as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found associated with white matter dysmaturation as shown by the immunohistochemical profiles and microarrays analyses. Strikingly, transcriptomic and gene network analyses reveal not only a myelination deficit in growth-restricted pups, but also the extensive deregulation of genes controlling neuroinflammation and the cell cycle in both oligodendrocytes and microglia. Our findings shed new light on the cellular and gene regulatory mechanisms mediating brain structural and functional defects in malnutrition-induced FGR, and suggest, for the first time, a neuroinflammatory basis for the poor neurocognitive outcome observed in growth-restricted human infants. GLIA 2016;64:2306-2320.
