Expression Of Brain-derived Neurotrophic Factor And Its Receptor In Polycystic Ovary Syndrome Rats

Objective Polycystic ovary syndrome(PCOS) is the most common and highly heterogeneous endocrine and metabolic disorders in adolescence and women of reproductive age. The main clinical manifestations are Oligomenorrhea and infertility, androgen excess symptoms, obesity and insulin resistance. What’s worse, type 2 diabetes, cardiovascular disease and endometrial cancer are the long-term complications. Abnormal endocrine and paracrine factors, metabolic dysfunction and the altered follicle micro environment may combinationally cause follicular developmental disorders. In recent years, Brain-derived neurotrophic factor(BDNF), as a normal physiological regulator, plays an important role in follicular development, oocytes maturation and early embryo growth. By establishing PCOS animal model, we investigate the altered expression of BDNF and its receptor tyrosine kinase receptor B(Trk B) in letrozole-induced PCOS rats, to reveal the main pathophysiological mechanism of follicular obstacles in PCOS patients from molecular level.Methods PCOS rat model was induced by letrozole. Forty female rats were divided into two groups, with the model group given letrozole(1mg·kg-1·d-1, dissolved in 1% carboxymethyl cellulose) and the control group just 1% carboxymethyl cellulose by gavage administration for consecutively 21 days. Vaginal smear with giemsa staining was examined during gavage at the same time everyday, to monitor changes of rats oestrous cycle. After modeling serum sex hormone levels were determined by radioimmunoassay, the histologicchanges in ovaries were observed by Hematoxylin-eosin staining, the expression of BDNF and Trk B m RNA in ovary tissues was detected by real-time PCR, the expression of BDNF and Trk B protein was measured by Western blot, and the location of Trk B in ovarian tissue and the expression in different follicles were detected by immunohistochemistry. SAS 9.0 statistical software was used to analyze the results, denoted as x ±s. Independent-Samples T test was adopted to compare the results between two groups. α=0.05 is the inspection level, and P < 0.05 stands for statistically significant difference.Results Eighty percent of letrozole-induced PCOS rats perfomed irregularity of oestrous cycle. The serum testosterone(T), follicle-stimulating hormone(FSH) and luteinizing hormone(LH) levels in model group were markedly increased than those in control group(P<0.05), but estradiol(E2) and progesterone(P) in model group showed a considerable reduction(P<0.05). When compared with control group, model group rats showed increased ovarian volume and high incidence of subcapsular ovarian cysts together with decreased number of corpora lutea. The expression of BDNF m RNA was significantly higher in model group than that in control group(P<0.05), but the expression of Trk B m RNA reduced(P<0.05). BDNF and Fl-Trk B protein expressed in the ovaries of the model group were notably higher than the control group while tr-Trk B showed obviously lower than the control group, all with statistical significance(P < 0.01). The expression of Trk B in granulosa cells and oocytes between model group and control group differed in follicles. The variance in large preantral and cystic follicles showed statistical significance. Trk B expressed in granulosa cells of different follicles displayed no significant difference, while in the oocyte showed a trend of decreasing, with the strongest expression in primordial follicles and the gradually weakened expression along with the growth of follicles.Conclusion The rat model is proved to be an ideal PCOS animal model to study the pathophysiology of PCOS. The different expression of BDNF and Trk B in ovarian tissues may play a specific role on follicular developmental disorders in letrozole-induced PCOS rats. The expression of Trk B in oocyte decreases along with the maturation of follicles and difference between the model group and control group may indicate that BDNF/Trk B urgesfollicular developmental disorders in PCOS patients with an autocrine or paracrine manner.