Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease

Abstract

Abstract Background Polycystic ovary syndrome is a most common female reproductive disorder, involving endocrine and metabolic disorders with unclear etiology. Androgen-based rodent animal models like DHEA and DHT are most suitable for PCOS induction, but still, these models fail to produce non-lean PCOS phenotypes such as hyperandrogenism, hyperinsulinemia, elevated estrogen levels, and ovary weight. Excess fructose consumption leads to hyperandrogenism, hyperinsulinemia, and insulin resistance. The purpose of this study is to investigate, whether fructose consumption along with androgens in rats, could develop all metabolic and endocrine phenotypes of non-lean human PCOS disease.  Methods Prepubertal SD rats were administered with DHT (83ug, s.c.) and fructose (20%, p.o.) for 90 days whereas DHEA (7 mg/kg, s.c) and fructose (20%, p.o.) for 30 days. During study duration, the 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. The ovary, uterus, abdominal fat, and subcutaneous fat were collected and weighed, and histopathology was done for any anomaly’s findings. Results DHT + fructose-treated rats showed significant (p < 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 shows more cysts than the DHEA + F groups. No significant changes in uterine histology of DHT + F and DHEA + F-treated rats. Conclusion DHT + F-treated rats mimic all clinical phenotypes and could be used as novel rodent model for non-lean type PCOS.