Expression Of Anti-Mullerian Hormone In Three Rat Models Of Polycystic Ovary Syndrome

polycystic ovary syndrome(PCOS)is a common endocrine disorder in women of reproductive age, with a prevalence of 6-10%, characterized by anovulation, hyperandrogenism and polycystic ovaries. Anti-mullerian Hormone (AMH), also referred to as Mullerian inhibiting substance (MIS), is a member of the transforming growth factor-β family. AMH is produced by granulosa cells in ovary, and have an inhibitory action on primordial follicle assembly. It has been confirmed by many clinical studies that AMH level is 2-3 times higher in women with PCOS and is suggested to play an important role in the pathogenesis of PCOS. Because of the difficulty of sampling, it is of much more significance to find an ideal animal model with PCOS to do further research on AMH.Section I:Expression of AMH in latrozole PCOS rat modelObjective:PCOS is an endocrine disorder with high heterogeneity, which make it difficult to establish an animal model which can completely simulate its clinical and pathological manifestations. This part of the experiment is to evaluate PCOS rat model made with latrozole according to Rotterdam diagnostic criteria, and to study the expression pattern of AMH in this kind of model.Methods:6-week-old female Sprague-Dawley rats were administered by letrozole. Body weight, ovarian volume and weight, the estrous cyclicity was recorded. After modeling, Serum Steroid concentrations including FSH, LH, P, T, INS, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined.Results:The letrozole model group showed obvious hyperandrogenism, increased LH, decreased progesterone and polycystic ovary. In addition, the body weight, ovarian weight and volume of rats in model group were significantly higher than that in the control group. Serum AMH was increased in the model group and ovarian local AMH and AMH-RII were increased, too. A positive correlation was found between serum AMH and testosterone, serum AMH and growing follicles, while a negative correlation was found between serum AMH and body weight.Conclusion:The letrozole model group using adult rats was a successful PCOS model considering the morphology and endocrinology. Serum AMH and Ovarian local expression of AMH and AMH-RII were both increased. The increased serum AMH level in PCOS is the consequence of the androgen-induced excess of small antral follicles.Section II:Expression of AMH in levonorgestrel & hCG rat PCOS modelObjective:This part of the experiment is to evaluate levonorgestrel & hCG PCOS rat model according to Rotterdam diagnostic criteria, and to find the expression pattern of AMH in this kind of model.Methods:23-day-old female Sprague-Dawley rats were administered by levonorgestrel & hCG. Body weight, ovarian volume and weight, the estrous cyclicity were recorded. After modeling, Serum steroid concentrations including FSH, LH, P, T, INS, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined.Results:This kind of model showed obvious hyperandrogenism and polycystic ovaries. Ovarian weight and volume of rats in model group were significantly higher than that in the control group, but the body weight was not different between two groups. No significant correlation was found between serum AMH and other parameters.Conclusion:The levonorgestrel & hCG model group using young rats was a successful PCOS model according to Rotterdam criteria, and with higher AMH. The mechanism of AMH increased in ovarian needs further research.Section Ⅲ:Expression of AMH in prasterone sulfate sodium & hCG rat PCOS modelObjective:This part of the experiment is to evaluate prasterone sulfate sodium & hCG PCOS rat model according to Rotterdam diagnostic criteria, and to find the expression pattern of AMH in this kind of model.Methods:23-day-old female Sprague-Dawley rats were administered by prasterone sulfate sodium & hCG. Body weight, ovarian volume and weight, the estrous cyclicity was recorded. After modeling, Serum steroid concentrations including FSH, LH, P, T, INS, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined.Results:This kind of model showed increased ovarian volume and polycystic ovaries, without typical serum hormone characteristics. Ovarian local expression of AMH and AMH-RII were increased significantly and a positive correlation between serum AMH and body weight was observed.Conclusion:This model using young rats is a little bit more different from human PCOS and with low stability. The increased serum AMH level in PCOS may due to the excess of growing follicles.