Association Between Intestinal Zonulin Expression and Polycystic Ovary Syndrome in Rats

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder characterized by reproductive and metabolic disturbances, frequently associated with insulin resistance. Emerging evidence suggests that altered intestinal barrier function may be involved in the pathophysiology of PCOS, with zonulin recognized as a marker of increased intestinal permeability. This study aimed to investigate the association between PCOS and intestinal zonulin expression using an experimental animal model. The research was done on female Wistar rats. Animals were randomly assigned to a control group or a PCOS-induced group. PCOS was induced through androgen administration, after which intestinal zonulin expression was measured and compared between groups. Statistical analyses were performed to evaluate intergroup differences and the association between PCOS induction and zonulin expression. The results showed that PCOS-induced rats had significantly higher intestinal zonulin expression than controls (5.545 ± 1.163 vs. 3.775 ± 1.196; p < 0.001). Normality testing showed a non-normal distribution in the PCOS group (Shapiro–Wilk p = 0.027) and a normal distribution in controls (p = 0.413), supporting the use of non-parametric analysis. Mann–Whitney U test confirmed a significant difference between groups (U = 58.0, Z = −3.849), with a large effect size (r = 0.61). Structural modeling (SEM-PLS) demonstrated a significant direct effect of PCOS induction on zonulin expression (T = 9.797, p < 0.001), with substantial explanatory power (adjusted R² = 0.511) and predictive relevance (Q² = 0.371). The results demonstrated that PCOS-induced rats exhibited significantly increased intestinal zonulin expression compared with healthy controls. Further analysis revealed a significant positive correlation between PCOS induction and elevated zonulin expression, suggesting altered intestinal barrier function, as inferred from the heightened zonulin levels in the PCOS model. These findings suggest that PCOS is associated with increased intestinal permeability, supporting the involvement of gut barrier dysfunction in the metabolic features of the disorder. Intestinal zonulin expression may serve as a possible biomarker linked to metabolic disturbances, including insulin resistance, as indicated by previous studies and corroborative findings. This study provides experimental evidence highlighting the relevance of the gut–endocrine axis in PCOS pathophysiology and may contribute to the development of novel diagnostic or therapeutic strategies.