SAT-178 - Quantitative Characterization of A Dihydrotestosterone-Induced Mouse Model of Polycystic Ovary Syndrome using Whole-Ovary 3D Imaging and Metabolic Profiling

Background and

Aim:
Polycystic ovary syndrome (PCOS) affects approximately 10–15% of women of reproductive age and is a leading cause of anovulation and infertility. PCOS is frequently accompanied by hyperandrogenism, insulin resistance, and altered body composition. Androgen-induced mouse models reproduce key reproductive and metabolic features of PCOS and are widely used in translational research. However, conventional ovarian histology relies on sectional sampling and semi-quantitative estimates of follicle number and size, limiting accurate assessment of especially antral follicular dynamics. This study aimed to characterize a dihydrotestosterone (DHT)-induced mouse model of PCOS using reproductive and metabolic endpoints, using whole-ovary 3D imaging as a fully quantitative method to assess ovarian morphology.

Methods:
Female C57BL/6JRj mice were implanted subcutaneously at four weeks of age with slow-releasing DHT pellets (40 µg/day) or empty implants and maintained on a Western diet. After eight weeks of androgen exposure, mice received vehicle daily injections for four weeks prior to termination to mimic pharmacotherapy. Endpoints included body weight, body composition, anogenital distance, estrous cycle monitoring, and metabolic and endocrine plasma biomarkers. At termination, ovaries were imaged ex vivo using whole-ovary 3D light sheet fluorescence microscopy (LSFM) imaging, enabling complete volumetric reconstruction and absolute quantification of ovarian structures.

Results:
DHT-treated mice exhibited a rapid and sustained increase in body weight, fat and lean tissue mass and anogenital distance, confirming androgenization. Estrous cyclicity was completely disrupted, with no animals entering estrus during the monitoring period. DHT-treated mice showed impaired glycemic control with elevated fasting glucose and insulin levels. Whole-ovary 3D imaging confirmed anovulation by the absence of corpora lutea and enabled unbiased quantification of follicular populations. DHT-PCOS mice displayed a marked increase in the number of large antral follicles and thinning of the granulosa cell layer compared with controls which confirm PCOS-like ovarian morphology.

Conclusion:
The DHT-induced PCOS mouse model recapitulates key reproductive, metabolic, and androgenic features of PCOS. Whole-ovary 3D LSFM imaging provides a robust, fully quantitative assessment of ovarian morphology and represents a powerful translational tool for evaluating therapeutic interventions targeting PCOS.

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