The Effect Of The Polydatin On Polycystic Ovary Syndrome And Its Mechanisms

Objective: This paper aims to investigate the potent mechanisms of the effect of Polydatin on reducing hyperinsulinemia,improving insulin resistance,relieving hyperandrogenemia and promoting development of follicles in PCOS mice model,and then provide a new idea for the prevention and treatment of PCOS patients,furthermore,provide new clues for assisted reproductive treatment means in clinical,such as in vitro fertilization-embryo transfer(IVF)and intracytoplasmic sperm injection(ICSI).Methods: In the initial of this study,we successfully induced PCOS mice model by administering DHEA to immature female C57BL/6 mice,and then treated the PCOS mice with different dose of Polydatin after modeling.The control mice were given normal saline(NS)in the same volume.OGTT was measured just after the whole treatment,the levels of E2,LH,FSH,T and INS in serum were detected by ELISA;IHC method was used to detect the expression level of protein 3?-HSD and StAR in the ovary of PCOS mice;the expression level of androgen related gene CYP11a1,CYP17a1 and NR4A1 in mice ovary were detected by RT-PCR;we measured the gene expression level of CYP11a1,CYP17a1,3?-HSD,StAR and NR4A1 in primary theca cells extraction from mice ovary.Results: Polydatin at different doses(5mg/Kg,10mg/Kg)were administered to PCOS mice,respectively,after 21 days of administration,the defference of the body weight and serum FSH concentration of PCOS mice is not significantly,but the serum E2 and serum T concentration decreased obviously(P<0.05);In addition,Polydatin played and important role in reducing serum insulin level in PCOS mice and the difference was statistically significant(P<0.01),the analysis of insulin resistance index also confirmed at this point,there was a significant difference in insulin resistance index between the control group and the two Polydatin intervened group(P<0.001);But the serum LH concentration did not change significantly.The Ovary follicle count results showed that the number of primary follicles in Polydatin treated groups decreased,and the count of secondary follicles and follicles in more mature stage was significantly increased Polydatin groups(P<0.05).IHC results suggested that the protein secretion of StAR and 3?-HSD decreased in the of Polydatin treated mice(P<0.05),the expression of CYP11a1 and NR4A1 gene was also down-regulated,the gene CYP17a1 expression level decreased significantly at 5mg/Kg group(P<0.01),but had no change at 10mg/Kg group.Consistent with that,Polydatin significantly down-regulated the expression of androgen-related genes CYP11a1,CYP17a1,3?-HSD,StAR and NR4A1 in primary theca cells extraction from mice,and the difference between the control group and the Polydatin group was statistically significant(p<0.05).Conclusion: These results illustrated that,on the one hand,Polydatin could reduce the level of serum insulin in PCOS mice and alleviate the insulin resistance,reduce the expression of androgen-related protein,decrease the androgen synthesis in PCOS mice by down-regulating the expression of androgen-related genes(CYP11a1,CYP17a1,3?-HSD,StAR and NR4A1)in theca cells in PCOS mice ovary;On the other hand,Polydatin could reduce the recruitment of primordial follicle and promote the development and maturation of follicles of PCOS mice,so as to achieve goals of treating metabolic syndrome,improving follicular maturation disorder and improving follicle quality and reproductive capacity in PCOS mice,thus providing a new perspective for the exploration of the pathogenesis of polycystic ovary syndrome.