Prenatal morphine exposure induces molecular and structural alterations in the developing hippocampus of neonatal rats

Articles in Press

Document Type : Original Article

Authors

1 Student Research Committee, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran

2 Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran

3 Department of Hematology, Tehran University of Medical Science, Tehran, Iran

4 Department of Anatomical Sciences, Faculty of Medicine, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran

10.22038/ijbms.2025.90146.19436

Abstract

Objective(s): Prenatal exposure to opioids such as morphine poses significant risks to fetal neurodevelopment, particularly in brain regions critical for cognition, such as the hippocampus. Despite the prescription and use of opioids during pregnancy, the molecular and histological consequences of such exposure remain insufficiently explored. To evaluate the effects of short-term prenatal morphine exposure on the expression of key neurodevelopmental genes and the structural integrity of the hippocampus in neonatal rats.
Materials and Methods: Pregnant Sprague Dawley rats were administered intraperitoneal injections of morphine sulfate (10 mg/kg) on gestational days 15 and 16. On postnatal day 12, offspring (n = 6 per group) were euthanized, and their hippocampal tissues were collected. Quantitative real-time PCR was performed to assess the expression levels of neurodevelopmental genes, including MDH2, Neurog1, and BDNF. Histological evaluations were conducted using hematoxylin and eosin and cresyl violet staining to assess cellular architecture and neuronal viability. Immunohistochemical staining for GFAP, S100, and synaptophysin was used to evaluate astrocytic integrity and synaptic density.
Results: The morphine-exposed group showed significant up-reglation of MDH2, Neurog1, and BDNF (P<0.05). Histological analyses revealed neuronal degeneration and inflammatory infiltration in the hippocampus. Immunohistochemistry demonstrated a marked reduction of GFAP, S100, and synaptophysin signals, indicating substantial glial loss and synaptic disruption.
Conclusion: Prenatal morphine exposure leads to marked molecular and histopathological changes in the developing hippocampus, suggesting long-term risks for neurocognitive dysfunction. These findings emphasize the importance of limiting opioid use during pregnancy and identifying molecular targets for future therapeutic interventions.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 16 December 2025

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