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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 \u00b1 2.68 vs. 9.50 \u00b1 0.64), CA2 (20.75 \u00b1 1.03 vs. 8.25 \u00b1 1.10), CA3 (20.50 \u00b1 1.65 vs. 8.50 \u00b1 1.04), and DG (28.25 \u00b1 1.88 vs. 13.00 \u00b1 1.29) regions of the hippocampus than controls (P &lt; 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.<\/jats:p>","DOI":"10.5812\/ijem-167083","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:57:01Z","timestamp":1790056621000},"update-policy":"https:\/\/doi.org\/10.5812\/crossmark_update_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disturbed Spatial Learning and Hippocampal Molecular and Histological Alterations in Middle-Aged Rats with a History of Polycystic Ovary Syndrome"],"prefix":"10.5812","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4561-8472","authenticated-orcid":true,"given":"Mahsa","family":"Noroozzadeh","sequence":"first","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of 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Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pouria","family":"Mousapour","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Amiri","sequence":"additional","affiliation":[{"name":"Midwifery and Reproductive Health Department, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Jorjani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Neurobiology Research Center ,School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-065X","authenticated-orcid":true,"given":"Fahimeh","family":"Ramezani Tehrani","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 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