Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries(Patel, 2018). The etiology of PCOS is multifactorial, involving genetic, environmental, and lifestyle factors(Escobar-Morreale, 2018). Among the various pathophysiological mechanisms, chronic low-grade inflammation has emerged as a significant contributor to the development and progression of PCOS(Dabravolski et al., 2021; Rudnicka et al., 2021). Elevated levels of pro-inflammatory cytokines such as TNF-α, IL-6, and CRP have been reported in women with PCOS, suggesting an ongoing immune activation that may contribute to insulin resistance, ovarian dysfunction, and anovulation(Orisaka et al., 2023). Chronic inflammation has also been shown to disrupt folliculogenesis and promote androgen excess, further aggravating PCOS symptoms(Wang et al., 2020). These findings highlight the importance of immune regulation in PCOS pathophysiology(Wang et al., 2023), that immune dysregulation may exacerbate the metabolic and reproductive abnormalities observed in PCOS(Zhu et al., 2021; Shabbir et al., 2023). Identifying molecular players involved in immune modulation is essential to understanding PCOS pathology and could pave the way for targeted therapeutic approaches.

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein known for its role in modulating insulin-like growth factor (IGF) signaling, cellular senescence, and vascular remodeling(Evdokimova et al., 2012). Recent studies have expanded our understanding of IGFBP7, highlighting its involvement in immune processes. IGFBP7 has been implicated in tumor immune evasion, where its high expression in certain cancers is associated with poor prognosis due to its ability to inhibit T cell activation and promote an immunosuppressive tumor microenvironment (Rupp et al., 2015; Li et al., 2023a). Conversely, IGFBP7 has also demonstrated anti-tumor properties by enhancing T cell infiltration and reducing tumor growth in specific contexts(Benatar et al., 2012; Yi et al., 2022). Additionally, IGFBP7 is known to influence T cell subsets and migration(Liu et al., 2012; Tibbitt et al., 2019; Li et al., 2023b), further underscoring its multifaceted role in immune regulation.

Given IGFBP7's involvement in insulin signaling, immune modulation, and inflammatory pathways, all of which are disrupted in PCOS, there is a compelling rationale to investigate its role in PCOS pathophysiology(Chen et al., 2024). We hypothesize that IGFBP7 may modulate immune dysregulation in PCOS through its effects on T cell function, cytokine balance, and immune cell migration. Exploring IGFBP7's impact on immune responses in PCOS could yield new insights into the underlying immune mechanisms and identify novel therapeutic targets for PCOS management.

In this study, we sought to elucidate the role of IGFBP7 in the immune regulation of PCOS-like symptoms using IGFBP7 knockout (KO) mice. We employed a DHEA-induced PCOS mouse model, a widely used experimental model that closely mimics the endocrine and reproductive features of human PCOS(Motta, 2010). By analyzing spleen transcriptome and TCR β CDR3 repertoire in both wild-type and IGFBP7−/− mice within the DHEA-induced PCOS model, we aimed to elucidate the role of IGFBP7 in modulating immune responses associated with PCOS. Our results provide new insights into how IGFBP7 influences immune dysregulation in PCOS, and identify potential therapeutic targets for improving the management of this condition.