Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Sara Torstensson; Angelo Ascani; Sanjiv Risal; Haojiang Lu; Allan Zhao; Alexander Espinosa; Eva Lindgren; Johansson Maria H; Gustaw Eriksson; Maya Barakat; Karlsson Mikael CI; Camilla Svensson; Anna Benrick; Elisabet Stener-Victorin

doi:10.1530/ey.22.14.17

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 14.17 | DOI: 10.1530/ey.22.14.17

ESPEYB25 14. The Year in Science and Medicine Other Topics (4 abstracts)

14.17. Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Sara Torstensson , Angelo Ascani , Sanjiv Risal , Haojiang Lu , Allan Zhao , Alexander Espinosa , Eva Lindgren , Maria H Johansson , Gustaw Eriksson , Maya Barakat , Mikael CI Karlsson , Camilla Svensson , Anna Benrick & Elisabet Stener-Victorin

Advanced Science. 11, 2401772 (2024). doi: 10.1002/advs.202401772

Brief Summary: In a PCOS-like mouse model, this study uses a combination of flow cytometry, ELISA, and metabolic phenotyping to show the effect of hyperandrogenism on immune cell populations in a tissue-specific manner. Androgen exposure caused a decrease of eosinophils in the uterus and visceral adipose tissue as well as a higher frequency of natural killer cells and elevated levels of IFN-γ and TNF-α in the uterus. Using an androgen receptor antagonist, these results were mitigated, leading to the conclusion that these effects were dependent on androgen receptor activation.

Despite the PCOS-like mice having an altered immune profile in visceral adipose tissue, as well as a higher body weight, their fat mass was unaltered compared to control mice. Moreover, androgen-exposed mice were insulin-resistant, mimicking a common PCOS-like trait.

These findings show that hyperandrogenism directly influences immune cell composition in reproductive and metabolic tissues leading to impaired tissue function. Moreover, the immunological disturbances discovered in androgen-exposed mice provide insight into how PCOS and low-grade inflammation are associated with each other. The study highlights the importance of considering immune dysregulation in PCOS pathophysiology and suggests that targeting androgen receptor signaling could be a therapeutic target to mitigate both reproductive and metabolic complications in PCOS patients.

Limitations: The study is based on a mouse model; thus human validation is needed. The exact mechanisms by which AR signaling indirectly affects non-AR-expressing immune cells remain unclear and the functional consequences of immune alterations on fertility and metabolism were not directly tested.