MON-228 FSH/AMH Ratio and Adipocyte Size Are Important Indicators for Ovarian Cyst Formation

Abstract

Abstract High-fat, high-sugar (HFHS) diet induces a number of metabolic dysfunctions. Furthermore, there is evidence that diet-induced obesity correlates with diminished reproductive outcomes, though the mechanism remains unclear. We utilized a female, HFHS rat model to determine the effects of adiposity on ovarian morphology and hormonal balance. Because animals were on an ad libitum diet, we observed a gradient of obesity and adiposity, as well as ovarian dysfunction. We explored the distribution of these variables in order to establish a potential mechanism for reproductive dysfunction in our HFHS model. To determine the effect of a HFHS diet on ovarian structures, adiposity, and follicle-relevant hormones, female Sprague-Dawley rats were separated into two diet groups. The control group (n=14) received standard chow and water ad libitum while the HFHS group (n=16) received 60% of calories from fat, 30% sucrose solution, and water ad libitum. Weights were recorded every other day, and estrous cycles were monitored through daily vaginal cytology. During the course of the study, a fraction of animals ceased cycling. Terminal blood samples were taken on diestrus-2. AMH and FSH levels in the plasma were measured using ELISA. Ovaries and abdominal fat pads were collected and sectioned for histological analysis. At the conclusion of the study, HFHS rats gained significantly more weight than controls and displayed larger abdominal and gonadal fat pads. Rats were divided into three groups based on estrous cycle status: non-cycling (n=7), HFHS cycling (n=8), and control cycling (n=7). Non-cycling and HFHS rats displayed different distributions in adipocyte size relative to controls, indicating a shift towards larger cell size. On average, non-cyclers and HFHS had more cysts then controls, and non-cyclers had fewer corpora lutea compared to HFHS and controls. While AMH and FSH levels did not differ between groups, the ratio of FSH to AMH significantly correlated with follicular structures. The FSH/AMH ratio displayed strong negative correlations with total follicle number (r=-0.72, p<0.0005) and late antral follicles (r=-0.78, p<0.00005), also correlating positively with the number of cysts per section (r=0.74, p<0.001). Independently, adipocyte size was also predictive of cysts per section (r=0.49, p<0.02). Taken together, however, the FSH/AMH ratio and adipocyte size strongly predicted number of cysts per section in multiple regression. Our results suggest that morphological changes resulting from diet-induced obesity occur along a spectrum, modulated by hormonal balance and adiposity. These results establish the FSH/AMH ratio and adipocyte size as important markers for the onset of ovarian dysfunction, particularly cyst formation. In addition, the FSH/AMH ratio predicts follicle counts in the ovary, providing a combined measure for prediction of follicle status.