Expression Of SIRT1,Fox03a,NRF-1 And SIRT6 In Ovarian Tissue Of DHEA Induced Rat Model With Polycystic Ovarian Syndrome And Its Implication

background: Polycystic ovary syndrome(PCOS)is the most common endocrinopathy and one of the most frequent causes of infertility in women of reproductive age.It is a heterogeneous syndrome with the characteristics of hyperandrogenemia,anovulation,dyslipidemia,and Menstrual dysfunction.The incidence of PCOS in women of reproductive age is up to 5-10%.Although PCOS was described almost eighty years ago,the etiology of PCOS still remains unclear,an interaction of environmental and genetic factors may contribute to the pathological process of the disease.Silent information regulator 1(SIRT1)is a NAD+ dependent histone deacetylase which are emerging as key factor related to cellular processes,including gene expression,cell differentiation,energy metabolism,oxidative stress response,apoptosis,DNA repair and senescence.Moreover,recent studies have implicated that SIRT1 is associated with inflammation and immune response.In addition,SIRT1 also can promotes insulin secretion and affects lipid and glucose metabolism.Forkhead-box transcription factor 3a(Fox O3a)is a significant substrate of SIRT1,and Fox O3 a transgenic mice shows sexual maturity delayed and follicle development inhibited.Nuclear respiratory factor 1(NRF-1)is a mediator of SIRT1,and it's known to regulate mt DNA replication and transcription in various tissues.A study demonstrated that SIRT1/Fox O3a/NRF1/SIRT6 effect ovarian follicle development and maturation by calorie restriction.Based on these data,we suppose that SIRT1,Fox O3 a,NRF1 and SIRT6 may play a potential regulatory role in PCOS patient's ovaries.Object: Set up an animal model of PCOS by using dehydroepiandrosterone(DHEA)and observe the expression of SIRT1,Fox O3 a,NRF-1 and SIRT6 in the ovaries of rats for investigating the pathogenesy of PCOS.Methods: Twenty female SD rats were randomly divided into normal control group and DHEA group.In the DHEA group,DHEA was injected subcutaneously for 20 days.The normal control group was given the same volume of sesame oil.The Oral glucose tolerance test(OGTT)were performed after treatment.Light microscopic examinations were performed.Serum T,LH,FSH,FINS and FPG levels in rats were determined with ELISA method.Serum HDL,LDL,TC and TG were detected by endpoint method.The expressions of SIRT1 and Fox O3 a in ovarian tissue were detected with immunohistochemistry and levels of SIRT1,Fox O3 a,NRF-1 and SIRT6 m RNA in ovarian tissue were measured with RT-PCR.Results: The PCOS rats exhibited increased volume of ovaries.In PCOS group,microscope showed a number of cysts formed from atretic follicle,and a diminished granulosa layer.The OGTT showed no significant difference between two groups.Serum levels of T,LDL and TG increased in the PCOS group,in contrast with the control group(P<0.05).The level of SIRT1 protein in ovaries of PCOS group was significantly higher than the control group(P <0.05).The level of Fox O3 a protein was increased in the ovaries of PCOS group but no significantly different(P = 0.071).The expression of SIRT1,Fox O3 a,NRF-1 and SIRT6 m RNA in the ovarian tissues of PCOS group increased significantly compared to the control group(p<0.05).Conclusion: SIRT1/FoxO3a/NRF-1/SIRT6 expressed in the ovaries may play a role in the process of PCOS by regulating granulosa.