THE POSSIBLE EFFECT OF FLAXSEED EXTRACT ON LETROZOLE-INDUCED POLYCYSTIC OVARY RAT MODEL: CORRELATIVE HISTOLOGICAL AND FUNCTIONAL STUDY

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common metabolic disorders affecting women in the reproductive age leading to infertility/subfertility. It may occur as a complication of Letrozole (LTZ) therapy in breast cancer patients. Objective: This was a preliminary study to assess the possible protective and/or curative effect of flaxseed extract in a letrozole-induced PCO rat model. Material and Methods: Thirty-six adult female albino rats were divided into five main groups: Group I kept as the control group, Group II (Letrozole-induced PCO group), received letrozole solution (3 mg/kg) orally once daily by gastric tube for 21 days. Group III (combined flaxseed and letrozole group), received aqueous flaxseed extract (500 mg /kg/day) orally one hour before letrozole in the same dose and duration as group II, Group IV (recovery group), received letrozole in the same dose and duration as group II and then left without treatment for the next 4 weeks after PCO induction, Group V (flaxseed-treated group), treated with aqueous flaxseed extract orally once daily for the next 4 weeks after PCO induction. At the end of the experiment, final body weight, ovarian weight, blood glucose, serum antioxidants assay, and sex hormones levels were measured. Also, specimens of ovaries were processed for light and electron microscopic studies. Histomorphometric and statistical analyses were done. Results: letrozole-induced PCO resulted in a significant increase in final body weight, ovarian weight as well as abnormal blood glucose, sex steroids hormone levels, and antioxidant assays. Moreover, numerous ovarian cystic follicles, widespread cytoplasmic vacuolation in the granulosa lutein cells, congested blood capillaries, and increased fibrosis within the ovarian medulla were evident in the PCO group in concomitant with a significant increase in area percentage of collagen fibers. The ultrastructural assessment confirmed these distortions. The protective and curative potential of flaxseed is mostly comparable revealed improvement in the final body weight, biochemical markers and histological changes, with the protective effect was more pronounced than the curative one. Conclusion and Recommendation: Flaxseed succeeded in ameliorating letrozole-induced polycystic ovary owing to its phytochemicals, antioxidant and anti-inflammatory properties with folliculogenesis potentials. So, it is recommended to use flaxseed as a co-therapy with letrozole to reduce its hyperandrogenic effects.