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Sex-dependent changes induced by prenatal stress in cortical and hippocampal morphology and behaviour in rats: an
1Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Centre, Ein Kerem, Jerusalem, Israel. martar@ekmd.huji.ac.il
Insights
Prenatal stress during pregnancy can lead to cognitive and emotional issues in offspring, with effects varying by sex. Maternal adrenalectomy prevents these negative outcomes, suggesting corticosterone
Area of Science:
- Neuroscience
- Developmental Psychology
- Reproductive Biology
Background:
- Gestational stress is linked to offspring cognitive and emotional deficits, particularly between weeks 12-20 of pregnancy.
- Potential gender-specific effects of prenatal stress on offspring development are suggested.
- Animal models offer insights into the mechanisms underlying these effects.
Purpose of the Study:
- To review recent studies on sex differences in behavioral and brain morphology changes in rats exposed to prenatal stress.
- To investigate the timing, intensity, and age-dependency of stress-induced effects.
- To explore the hormonal mechanisms mediating these sex-dependent outcomes.
Main Methods:
- Review of studies involving prenatal stress in rats during critical neurodevelopmental periods.
- Behavioral testing of offspring for learning deficits and anxiety.
- Analysis of brain morphology, including neurogenesis and dendritic structure in the prefrontal cortex and hippocampus.
- Intervention studies involving maternal adrenalectomy and corticosterone administration.
Main Results:
- Prenatal stress induced sex-specific behavioral changes: learning deficits in males and anxiety in females.
- These deficits correlated with reduced neurogenesis and altered dendritic morphology in the hippocampus and prefrontal cortex.
- Maternal adrenalectomy abolished anxiety and male learning deficits; corticosterone administration reinstated anxiety but not learning deficits.
Conclusions:
- Prenatal stress exerts sex-dependent effects on offspring neurodevelopment and behavior.
- Offspring anxiety appears to stem from fetal exposure to maternal corticosterone.
- Male learning deficits may involve reduced testosterone and aromatase activity, alongside other adrenal hormones.
Abstract:
Recent prospective studies have shown that gestational stress in humans is more likely to cause cognitive and emotional problems in the offspring if it occurs during weeks 12-20 of pregnancy. There are also suggestions that such problems may be gender dependent. This review describes recent studies that found sex differences in the behaviour and brain morphology of rats stressed prenatally during the equivalent period of neuronal development in humans. Learning deficits are more prevalent in males and anxious behaviour in females but their appearance depends also on the timing and intensity of the stress and the age when the offspring were tested. Cognitive deficits and anxiety are linked to a sex-dependent reduction in neurogenesis and in measures of dendritic morphology in the prefrontal cortex and hippocampal formation. Maternal adrenalectomy prior to the stress prevents the anxiety in both sexes and learning deficits in males. Corticosterone administration to the dam to mimic levels induced by stress reinstates only the anxiety, indicating that it arises from foetal exposure to corticosterone from the maternal circulation. Learning deficits in males may result from a combination of a reduction in testosterone and in aromatase activity, together with the action of other adrenal hormones.

