Effect of low doses of FSH and P4 on cystogenesis-induced mice as a polycystic ovary syndrome model

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, characterised by chronic hyperandrogenic anovulation and dys- regulation of reproductive hormones together with metabolic abnormalities. The aetiology of PCOS is still uncertain and cur- rent therapeutical treatments are moderately effective. Hence, appropriate animal models that mimic many or all PCOS traits can facilitate research, leading to improve understand- ing of the pathogenesis of PCOS and the potential for innovative approaches for its therapy. Several reports indi- cate that hyperandrogenisation can be induced in mice by dehyidroepiandrosterone (DHEA). DHEA-treated mice develop cysts and exhibit many of the salient features of human PCOS. Aim: To study the effect of a highly diluted and dynamised form of FSH and P4 on a DHEA-PCOS murine model. The morphology of antral follicle population and E2 and P4 serum concentrations were evaluated. Methods: Thirty-six female-prepubertal Balb/c mice were either injected for 20 consecutive days with DHEA (6 mg kg–1 body weight) dissolved in 0.1 ml sesame oil (DHEA group) or injected with DHEA and treated by oral administration with low dose of an activated solution of P4 plus FSH in saline solution (0.44 pg day–1 and 0.44 fg day–1 respectively, LD group). The solution was activated by shaking. A third group received only sesame oil (control group). Mice were then sacrificed, blood was collected for hormone analysis (enzyme-linked immunosor- bent assay (ELISA)) and ovaries were fixed for morphological studies. Results and conclusion: Histological examination revealed an increase in the total number of antral follicles >300 m in diameter in both DHEA and LD groups compared with con- trols (p<0.05). However, LD treatment significantly reduced cystic/atretic signs in the follicles (p > 0.05). Finally, DHEA treatment increased both E2 and P4 serum levels compared with controls (p < 0.05). Nevertheless, LD administration decreased serum E2 to a level similar to controls. Conclusion: Our preliminary results indicate that low and activated doses of FSH and P4 are able to decrease the follicular alterations induced in DHEA-treated mice. This could represent a novel approach in reducing the severity of PCOS syndrome and its endocrine and reproductive complications.