Immunohistochemical Analysis and Role of Secreted Frizzled-Related Protein-4 in Polycystic Ovary-Induced Rat
Objective: The role of Wnt signaling and its antagonist; secreted Frizzled Related Protein type 4 (sFPR4) was reported in rodent ovarian follicular development. This study examines immunolocalization of sFRP4 in ovaries of polycystic ovary (PCO) rat model and evaluates its role in follicular growth arrest and its premature differentiation. Materials and Mathods: PCO was induced with daily administration of testosterone propionate (TP) for 1 to 4 weeks while normal control rats were injected only with vehicle. The ovaries underwent histological examination, immunohistochemical analysis of sFRP4 and steroidogenic acute regulatory protein (StAR) and apoptosis analysis. Results: Four-week TP treatment significantly increased the primordial follicles, and significantly decreased the preantral and antral follicles compared to one week TP treatment. TP-treated animals had concomittantly, significant increase of sFPR4 immunoexpression in primordial, primary and preantral follicles as compared to one week TP-treated animals and control groups. Furthermore, sFRP4 immunostaining strongly co-localized in apoptotic granulosa cells. Interestingly, increased sFRP4 immunostaining was associated with increased StAR immunoexpression in follicular theca layer and stroma in four weeks TP-treated rats compared to one week TP-treated rats and control groups. Conclusion: Our data showed a highly significant association between sFRP4 expression and apoptosis in ovaries of four week TP-treated animals. Moreover, co-localization of StAR and sFRP4 could suggest that sFRP4 may play a role in premature differentiation of follicles.