Defective Hippocampus-Dependent Spatial Memory in Mouse Model of Polycystic ovary syndrome

Abstract Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disorder characterised by hyperandrogenism, oligo- or anovulation, and polycystic ovaries. Endocrine dysfunction in PCOS disrupts both hormonal and neurotransmitter balance, contributing to the psychological distress frequently reported by affected individuals. Although hormonal imbalances have been associated with memory impairments, their specific contribution to cognitive dysfunction in PCOS remains incompletely understood. In this study, we investigated the impact of PCOS on the hippocampus, a brain region critical for memory formation and highly sensitive to sex steroid modulation. A dehydroepiandrosterone (DHEA)-induced PCOS mouse model was employed to assess anxiety-like behaviour, locomotion, and memory. In the open field test (OFT), DHEA-treated mice spent significantly less time in the central zones and travelled a shorter total distance compared with controls, indicating increased anxiety-like behaviour. DHEA treatment also resulted in significantly impaired performance in both the object location test (OLT) and novel object recognition test (NORT), as reflected by a reduced discrimination index. Analysis of hippocampal immediate early gene expression using qRT-PCR revealed altered transcription of memory-related markers, including downregulation of Npas4 and Grin2a, and upregulation of Grin1, Arc, Egr1, and Egr2. Collectively, these findings suggest that elevated androgen levels induce anxiety- and depression-like behaviours and impair cognitive function, including spatial, recognition, and motor learning abilities, in PCOS. Our results further indicate that disrupted cortex–hippocampus communication may underlie these cognitive deficits, underscoring the importance of evaluating memory and cognitive health in women with PCOS to support brain health and overall well-being. Competing Interest Statement The authors have declared no competing interest. Data availability The data generated for the study underlying this article are available in the article and in its online supplementary material. The data will be shared on reasonable request to the corresponding author.