MON-190 T Cells Are Necessary For The Development Of Reproductive Impairments In A Letrozole-induced Mouse Model Of Polycystic Ovary Syndrome

Abstract Disclosure: N. Ujagar: None. G. De Robles: None. C. Nguyen: None. K.D. Wiggins: None. Z. Del Mundo: None. J. Cassin: None. J. Kim: None. N. Naidu: None. J.A. Ayala Angulo: None. B. Babaev: None. R.A. Ross: None. A.S. Kauffman: None. V.G. Thackray: None. B. Banaszewska: None. E. Wysocka: None. A.J. Duleba: None. M. Seldin: None. D. Nicholas: None. Polycystic ovary syndrome (PCOS) is a complex reproductive disorder with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PCOS, but a clear cause-and-effect relationship has yet to be established. This study employed a comprehensive systems immunology approach, utilizing a letrozole-induced PCOS mouse model to identify changes in inflammatory factors associated with PCOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified TNF-β as a key T cell-derived cytokine associated with PCOS, regardless of genetic background. We confirmed elevated TNF-β transcripts in immune cells from women with PCOS. Importantly, we used a knockout of TCRα to show that functional T cells are a necessary component of driving PCOS features in letrozole-treated female mice. These findings implicate T cells, and specifically TNF-β production. in the development of PCOS associated impairments. T cells are therefore an attractive target for the future development of anti-inflammatory therapeutics to improve PCOS symptoms. Presentation: Monday, July 14, 2025