Development and evaluation of rodent model of pcos mimicking clinical phenotypes in human disease

Abstract

Material and Methods: Prepubertal SD rats were administered with DHT (83ug, s.c.) and fructose (20%, p.o.) for 90 days whereas DHEA (7mg/kg, s.c) and fructose (20%, p.o.) for 30 days. Ovajal was orally dosed at 100mg/kg and 200 mg/kg. During study duration, blood glucose level for oral glucose tolerance test, estrus cyclicity and ultrasonography was observed. Reproductive hormones LH, FSH, insulin, testosterone and estradiol levels were assessed using ELISA. Ovary, uterus, abdominal fat, and subcutaneous fat were collected, weighed and histopathology was done for any anomaly s findings. newline newline newlineResults and Discussion: DHT+ fructose treated rats showed significant (p lt 0.05) increase in serum testosterone, LH, estradiol, decreased FSH levels and caused multiple cystic follicles. Abdominal fat, subcutaneous fat, ovary, and uterine weight were higher in DHT+F and DHEA+F when compared to control groups. OGTT reveals impaired insulin sensitivity and glucose tolerance in both model groups. Ovarian histopathology of DHT+F show more cysts than DHEA+F groups. No significant changes in uterine histology of DHT+F and DHEA+F treated rats. In OV100and200 reversed the DHT-fructose induced changes by significantly (plt0.05) increasing serum FSH levels and decreasing body weight, ovary, uterine weight, luteinizing hormone, testosterone, estradiol serum levels, area under curve of glucose in oral glucose tolerance test, irregular estrous cyclicity and cystic follicles. However, the OV200 more effectively ameliorated the abnormalities of PCOS and showed significant effect to the first line drugs i.e., metformin and clomiphene citrate. newlineConclusion: From findings, it can be concluded that DHT+F treated rat s mimics all clinical phenotypes and could be used as novel rodent model for non-lean type PCOS. Ovajal formulation was effective in the management of experimental PCOS and hence may be recommended in the treatment of PCOS.