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Updated: Feb 19, 2026
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive impairment in male offspring after
Wanting Dong1, Dan Xu2, Zewen Hu1
1Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Insights
Prenatal dexamethasone exposure in rats leads to cognitive impairment in male offspring. This intrauterine programming affects the hippocampus, impacting learning and memory through the CREB/BDNF/TrkB pathway.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Adverse intrauterine environments are linked to neuropsychiatric disorders.
- Prenatal exposure to substances can alter offspring neurodevelopment and cognitive function.
Purpose of the Study:
- To investigate cognitive impairment in male offspring rats following prenatal dexamethasone exposure (PDE).
- To explore the intrauterine programming mechanisms underlying PDE-induced cognitive deficits.
Main Methods:
- Pregnant Wistar rats received dexamethasone injections during critical gestational periods.
- Offspring were assessed for cognitive function, hippocampal cellular changes, and molecular pathway alterations.
- Fetal and adult male offspring hippocampi were examined for structural and functional changes.
Main Results:
- Adult male offspring exposed to PDE exhibited significant cognitive impairment.
- PDE resulted in decreased hippocampal cell proliferation, increased apoptosis, damaged synaptic plasticity, and disrupted protein synthesis.
- Activation of the glucocorticoid receptor (GR) and downregulation of the CREB/BDNF/TrkB signaling pathway were observed in PDE offspring.
Conclusions:
- Prenatal dexamethasone exposure causes cognitive impairment in adult male rat offspring.
- The underlying mechanism involves the programming of the hippocampal CREB/BDNF/TrkB signaling pathway, leading to impaired cognitive function.
Abstract:
Adverse intrauterine environments can increase susceptibility to neuropsychiatric diseases that are related to cognitive impairment. In this study, we observed the cognitive impairment of male offspring rats after prenatal dexamethasone exposure (PDE) and explored the associated intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously injected with 0.2mg/kgd dexamethasone from gestational day 9 (GD9) to GD20. A cohort of the pregnant rat group was sacrificed on GD20, and the male fetal rats were collected. Another group of pregnant rats delivered their offspring naturally, and the male adult offspring rats were subjected to behavioural tests postnatally at 26 weeks and then sacrificed. The adult PDE male offspring rats exhibited cognitive impairment, decreased cell proliferation and increased cell apoptosis in the hippocampus, along with damaged synaptic plasticity and disrupted protein synthesis. Meanwhile, activation of GR and downregulation of the cAMP responsive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin receptor tyrosine B (TrkB) signalling pathway were found in the adult PDE offspring rats. Further examinations indicated consistent alterations to the fetal hippocampus by PDE. We concluded that PDE can cause cognitive impairment in adult male offspring rats. The mechanism may be associated with low-functional programming of the hippocampal CREB/BDNF/TrkB signalling pathway.
