Female hyperandrogenism increases vulnerability to pain and depression in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) stands out as the most prevalent reproductive disorder affecting women, impacting hormonal and metabolic equilibrium. It can manifest as hyperandrogenism, insulin resistance, anovulation, and infertility. PCOS is associated with various symptoms such as obesity, hirsutism, and acne, which, in turn, elevate the risk of conditions like endometrioma, type 2 diabetes, cardiovascular disease, and irritable bowel syndrome. Previous data from our research indicated that PCOS accelerates pain perception in patients, yet the underlying mechanism remains elusive.In this study, we employed spinal nerve ligation (SNL) to induce chronic pain and depression in a rat model of PCOS induced by letrozole. Our findings revealed that PCOS heightened behavioral outcomes related to pain sensitivity and depression, as assessed through the von Frey test, forced swimming test, tail suspension test, and open-field test. Additionally, enzyme-linked immunosorbent assay (ELISA) results demonstrated elevated levels of inflammatory cytokines TNF-alpha and IL-6 in PCOS rats. Moreover, immunofluorescent staining revealed increased accumulation of macrophages in adipose tissue, coupled with enhanced polarization towards the M1 type microglia in PCOS rats.