Unpacking PCOS Inflammation: From Misconceptions to Immune Networks.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting women worldwide. For decades, the "chronic inflammation hypothesis" has guided research into the role of the immune system in PCOS pathogenesis. However, this review challenges this paradigm by pointing out discrepancies in current literature on systemic immune markers in PCOS. We highlight the limitations of relying solely on systemic inflammatory markers and emphasize the importance and diversity of tissue-specific immune responses. Evidence from human and animal studies reveals distinct immune responses across various tissues affected by PCOS or inflammation, including the hypothalamus, pituitary, ovaries, endometrium, and adipose tissue. These findings suggest that PCOS is not characterized by systemic low-grade inflammation, but rather by discrete tissue-specific immune interaction with endocrine cells. Finally, we discuss how advanced single-cell technologies and computational tools are enhancing our understanding of immune cell signaling to endocrine cells in PCOS. Moving forward, we propose that research should focus on elucidating causal relationships between local immune responses and endocrine dysfunction in PCOS. This shift in perspective from systemic to tissue-specific immune responses is critical for developing targeted immunotherapies for PCOS.