Immunohistochemical analysis and role of secreted frizzled-related protein-4 in polycystic ovary-induced rat

ABSTRACT

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. 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. 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. 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