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Uteroplacental insufficiency alters rat hippocampal cellular phenotype in conjunction with ErbB receptor expression
Camille Fung1, Xingrao Ke, Ashley S Brown
1Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA. camille.fung@hsc.utah.edu
Insights
Uteroplacental insufficiency (UPI) causes neurodevelopmental deficits in intrauterine growth-restricted (IUGR) offspring, particularly in males. These deficits stem from altered hippocampal cell composition and molecular signaling, impacting brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Reproductive Medicine
Background:
- Uteroplacental insufficiency (UPI) leads to intrauterine growth restriction (IUGR), causing significant neurodevelopmental deficits, especially in the hippocampus.
- IUGR male offspring exhibit more severe hippocampal deficits than females, with underlying mechanisms remaining unclear.
- Altered hippocampal cellular composition and neural stem cell (NSC) differentiation molecule expression are potential contributors to IUGR-related neurodevelopmental issues.
Purpose of the Study:
- To investigate alterations in hippocampal cellular composition (neuronal, astrocytic, immature oligodendrocytic proportions) in IUGR offspring at birth.
- To examine the impact of UPI on the expression of ErbB receptors (ErbB-Rs) and neuregulin 1 (NRG1) in the rat hippocampus at birth and weaning.
- To determine if gender-specific cellular and molecular changes in the hippocampus correlate with IUGR-related neurodevelopmental deficits.
Main Methods:
- Utilized a validated rat model of IUGR induced by bilateral uterine artery ligation at embryonic day 19.5.
- Analyzed hippocampal cellular composition, including neuronal, astrocytic, and immature oligodendrocytic proportions, at birth.
- Assessed the expression of ErbB receptors and neuregulin 1 in the hippocampus at birth and weaning stages.
Main Results:
- IUGR offspring displayed altered hippocampal neuronal, astrocytic, and immature oligodendrocytic composition compared to gender-matched controls.
- These cellular alterations were found to be subregion- and gender-specific.
- UPI led to altered receptor type- and gender-specific expression of ErbB-Rs in the hippocampus at both birth and weaning.
Conclusions:
- Cellular alterations in the hippocampus, including changes in neuronal, astrocytic, and oligodendrocytic populations, contribute to IUGR-related neurodevelopmental complications.
- Aberrant expression of ErbB receptors and neuregulin 1 in the hippocampus may underlie both short- and long-term neurological sequelae of IUGR.
- The observed cellular and molecular changes provide a basis for understanding the increased susceptibility of male IUGR offspring to more severe neurological outcomes.
Introduction:
Uteroplacental insufficiency (UPI) produces significant neurodevelopmental deficits affecting the hippocampus of intrauterine growth-restricted (IUGR) offspring. IUGR males have worse deficits as compared with IUGR females. The exact mechanisms underlying these deficits are unclear. Alterations in hippocampal cellular composition along with altered expression of neural stem cell (NSC) differentiation molecules may underlie these deficits. We hypothesized that IUGR hippocampi would be endowed with altered neuronal, astrocytic, and immature oligodendrocytic proportions at birth, with males showing greater cellular deficits. We further hypothesized that UPI would perturb rat hippocampal expression of ErbB receptors (ErbB-Rs) and neuregulin 1 (NRG1) at birth and at weaning to account for the short- and long-term IUGR neurological sequelae.
Methods:
A well-established rat model of bilateral uterine artery ligation at embryonic day 19.5 was used to induce IUGR.
Results:
As compared with gender-matched controls, IUGR offspring have altered hippocampal neuronal, astrocytic, and immature oligodendrocytic composition in a subregion- and gender-specific manner at birth. In addition, IUGR hippocampi have altered receptor type- and gender-specific ErbB-R expression at birth and at weaning.
Discussion:
These cellular and molecular alterations may account for the neurodevelopmental complications of IUGR and for the male susceptibility to worse neurologic outcomes.
