A Rat Model of Polycystic Ovary Syndrome with Insulin Resistance Induced by Letrozole Combined with High Fat Diet

Abstract

BACKGROUND Clinically, most patients of polycystic ovary syndrome (PCOS) also have insulin resistance (IR). The methods for establishing PCOS-IR animal model include using dehydroepiandrosterone (DHEA) and sodium prasterone sulfate subcutaneous injection, testosterone propionate combined with high-fat diet, and so on. This study aimed to establish an animal model of PCOS-IR using letrozole combined with a high fat diet. MATERIAL AND METHODS Study rats received 0.5% carboxymethylcellulose solution (CMC) or letrozole solution (1 mg/kg/day), with normal diet as control group and a high fat diet as the model group, for 21, 24, 27, and 30 days. The body weight and length were measured weekly. On Day 22, 25, 28 and 31, the weight, and the short and long diameters of the rat ovaries were measured, and blood samples were collected for the measurement of fasting plasma glucose (FPG), fasting insulin (FINS), triglyceride (TG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T). Ovarian tissue was collected for paraffin sectioning and hematoxylin and eosin (H&E) staining. RESULTS In model groups, rats' weight was significantly increased (P<0.05). On Day 28 and 31, the weight, Lee's index, and ovarian volume significantly increased compared with Day 22 (P<0.05). There were more dense transparent saclike follicles on the ovary surface under the microscope in model groups. Levels of LH/FSH, T, and TG were substantially increased (P<0.05), but levels of FINS and HOMA-IR were significantly increased (P<0.05) on Day 28 and 31 in the model groups. CONCLUSIONS This study implied that letrozole combined with a high fat diet for 27 days could induce the PCOS-IR rat model which has the characteristics of ovarian polycystic changes and endocrine and metabolic disorders.

Figure 1

(A)The weight of rats between the 2 groups; (B) The Lee’s index of rats between the 2 groups; number, n=6, mean±standard deviation.

Figure 2

(A) The weight of rat ovarian between the 2 groups; (B) The volume of rat ovarian between the 2 groups; number, n=6, mean±standard deviation, * P<0.05 versus control group; ^# P<0.05 versus Day 22.

Figure 3

The change of rat ovarian tissue pathological in the 2 groups. (A) 50×, the ovarian of rats in the control group on Day 31; (B) 50×, the ovarian of rats in the model group on Day 22. (C) 50×, the ovarian of rats in the model group on Day 25; (D) 50×, the ovarian of rats in the model group on Day 28; (E) 50×, the ovarian of rats in the model group on Day 31; (F) 200×, the ovarian of rats in the control group on Day 31; (G) 200×, the ovarian of rats in the model group on Day 22; (H) 200×, the ovarian of rats in the model group on Day 25; (I) 200×, the ovarian of rats in the model group on Day 28; (J) 200×, the ovarian of rats in the model group on Day 31.

Figure 4

The differences in all kinds of follicles of rat ovarian tissue. (A) The number of cystic dilated follicles on the ovary surface of rats; (B) The number of atresia follicle on the ovary surface of rats; (C) The number of follicles in development stage in the ovaries of rats; (D) The number of corpus luteum in the ovaries of rats; number, n=6, mean±standard deviation, * P<0.05 versus control; ^# P<0.05 versus Day 22.

Figure 5

The levels of FPG, FINS, HOMA-IR and TG in rat serum. (A) The level of FPG in rats between the 2 groups; (B) The level of FINS in rats between the 2 groups; (C) The index of HOMA-IR in rats between the 2 groups; (D) The level of TG in rats between the 2 groups; number, n=6, mean±standard deviation, * P<0.05 versus control; ^# P<0.05 versus Day 22. FPG – fasting plasma glucose; FINS – fasting insulin; TG – triglyceride.

Figure 6

The levels of LH, FSH, LH/FSH and T in rat serum. (A) The level of LH in rats between the 2 groups; (B) The level of FSH in rats between the 2 groups; (C) The index of LH/FSH in rats between the 2 groups; (D) The level of T in rats between the 2 groups; number, n=6, mean±standard deviation, * P<0.05 versus control; ^# P<0.05 versus Day 22. LH – luteinizing hormone; FSH – follicle stimulating hormone; T – testosterone.