Tehran University of Medical Sciences

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Disturbed Spatial Learning and Hippocampal Molecular and Histological Alterations in Middle-Aged Rats With a History of Polycystic Ovary Syndrome Publisher



Noroozzadeh M ; Changaei M ; Farhadi Azar M ; Mousavi M ; Mousapour P ; Amiri M ; Jorjani M ; Ramezani Tehrani F
Authors

Source: International Journal of Endocrinology and Metabolism Published:2027


Abstract

Background: Studies have reported inconsistent findings regarding the potential effects of polycystic ovary syndrome (PCOS) on neurocognitive function. Objectives: This study aimed to investigate whether cognitive function, particularly spatial learning and memory, and hippocampal tissue are impaired in middle-aged rats with a history of PCOS. Methods: Spatial learning and memory, hippocampal histopathology, and the expression of genes including beta-secretase 1 (bace1), microtubule-associated protein tau (mapt), amyloid-beta precursor protein (app), nestin (nes), and doublecortin (dcx) in hippocampal tissue were compared between middle-aged PCOS rats and controls (n = 7/group). Results: During training (learning), middle-aged PCOS rats had significantly higher mean latency (22.04 (1.86, 42.22); P = 0.03) and duration (5.62 (1.41, 9.84); P = 0.009) than controls. However, memory performance did not differ significantly between PCOS rats and controls. PCOS rats had a significantly higher number of damaged neurons in the CA1 (24.25 ± 2.68 vs. 9.50 ± 0.64), CA2 (20.75 ± 1.03 vs. 8.25 ± 1.10), CA3 (20.50 ± 1.65 vs. 8.50 ± 1.04), and DG (28.25 ± 1.88 vs. 13.00 ± 1.29) regions of the hippocampus than controls (P < 0.05), and they showed mild hippocampal damage. In PCOS rats, bace1 gene expression was significantly increased in hippocampal tissue, whereas mapt gene expression was decreased compared with controls. The expression levels of the other genes did not differ significantly between the two groups. Conclusions: A history of PCOS during reproductive age may increase the risk of cognitive dysfunction, particularly impaired spatial learning, as well as hippocampal damage later in life. Copyright © 2026, Noroozzadeh et al. This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.