Microscopic Characterization of Follicular Structures in Letrozole-induced Polycystic Ovarian Syndrome in the Rat

Background: Our objective was to characterize the tissular distribution of relevant cytoskeletal proteins, cellular adhesion molecules and proliferation markers and conduct a histomorphometrical study of the follicular wall of letrozole-induced polycystic ovaries.

Methods: Twenty rats were divided into two groups: a control group (C) of ten rats that received vehicle only (0.9% NaCl solution) once daily p.o. and a treatment group (T) of ten animals administered letrozole at a concentration of 1 mg/kg p.o. dissolved in 0.9% NaCl solution once daily during 21 days. Twenty four h after the last administration, all animals were sacrificed. Control animals were sacrificed in proestrous (n = 5) and diestrous (n = 5). Serum hormone levels, histomorphometrical changes and immunoexpression of intermediate filaments (vimentin, cytokeratins and desmin), cadherins and proliferation cellular nuclear antigen were examined.

Results: The granulosa cell layer of cystic follicles had a greater significant immunostaining for vimentin and cytokeratins. Immunohistochemical localization of desmin was restricted to the theca externa. Positive immunoreactivity for cadherins rises gradually and significantly, together with the follicular development, and immunoreactivity was comparatively stronger in follicular cysts. A significantly higher immunostaining for PCNA cells was observed in secondary and tertiary follicles as compared with atretic and cystic follicles. An increase in the LH, FSH and testosterone serum concentrations was observed in letrozole-treated rats. Estradiol and progesterone showed a considerable reduction.

Conclusions: The changes observed are probably due to structural and functional alterations that occur during the process of cystogenesis and may be associated with important modifications in the expression of cytoskeletal proteins, cellular adhesion molecules and proliferation markers that may be essential for proper cellular functioning.