Serum Heat Shock Protein70,25Hydroxyvitamin D Levels And Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine andmetabolic disorder syndrome, which is characterized by chronic anovulation,hyperandrogenemia and polycystic ovaries. PCOS affect about5%-10%of premenopausalwomen.The specifically mechanisms of PCOS are very complex, and still remain unclear tillnow. Previous studies have shown that acute hyperglycemia causes an increase in thegeneration of reactive oxygen species (ROS), and PCOS patients are exhibited to oxidativestress in which increased production of free radicals and inflammatory mediators playimportant role. Some researches have also shown that metabolic abnormality andcardiovascular risk (such as diabetes and cardiovascular disease) factors related to PCOSare thought to be linked to insulin resistance. Besides insulin resistance, it is assumed thatlow grade chronic inflammation and oxidative stress may be the key centraletiopathogenetic factors in the pathophysiology of PCOS. However, duo tothe usual markers (such as MDA, TNF-a, CRP and IL-6) of oxidative stress andchronic inflammatory lack of specificity and sensitivity, it become the focus of currentresearch to looking for a highly sensitive and specific molecular marker and an effectiveintervention for PCOS.Heat shock proteins (HSPs) are a family of stress-responsive proteins that modulatecell function and contribute to protein homeostasis. HSP is highly conserved in all prokaryotic and eukaryotic cells, which generated by the heat shock genesencoding under high temperature or stress situations, also known as stress proteins. Themajor functions of HSP are involved in cell damage and repair. HSP70is the mostconservative, important and abundant protein in HSP family, which playing an importantrole in inhibiting free radical release and inflammatory cell infiltration, thus to improve thetolerance of the original stress. Studieshave confirmed the stability of the HSP70expression play an important role in the courseof the disease of chronic stress. Studies in diabetes patient manifest the increased level ofHSP70was time-dependent with the IR and beta cell damage, and HSP70is more sensitivethan other oxidative stress and inflammation indicators. The above evidences suggestHSP70could be used as a novel biomarker for oxidative stress in chronicsilicosis. However, this hypothesis has not been tested and verified in PCOS.In the other hand, except for the function in maintaining calcium and phosphorushomeostasis and promoting bone mineralization, vitamin D have also been reported tomodulate the reproductive processes in women. Studies have manifest that low25-hydroxyvitamin D levels are associated with obesity, metabolic and endocrinedisturbances in PCOS women, and proper vitamin D supplementation might improve thesedisturbances. However, the relationship between vitamin D associated with PCOS in ourcountry has not been reported.Therefore, we used the PCOS patients and non-PCOScontrols (withnormal ovulation) as the objects in this study, and aim to investigate therelationship between serum HSP70,25hydroxyvitamin D and PCOS. The main contentsinclude the following two sections: Part One Association between serum HSP70levels and PCOSObjective: to compare HSP70and the biomarkers of chronic inflammatory as wellas oxidative stress serum levels in PCOS patients and non-PCOS controls; to investigate theassociation between HSP70and choronic inflamation as well as oxcide stress; and toexplore the correlation between serum HSP70levels and PCOS.Methods: We uesd a case-control study to recruit PCOS patients and non-PCOScontrols as the objects, who took sex hormone test at the outpatient clinics of reproductivemedical center of Tongji Hospital affiliated to Tongji Medical College during the period ofNovember2011to April2012. The diagnosis of PCOS was established according to the2003Rotterdam criteria, and the controls have nomal ovulation corresponding to PCOS.Basic information of objects was collected by questionnaire.The serum concentrations oflipid profiles, glucose, insulin, NO, MDA, CRP, TNF-a and HSP70were detected.Results:(1) The individuals with PCOS, compared to non-PCOS controls, had higherlevels of TG, T, LH, INS, TNF-a, CRP, NO, MDA and HOMA-IR (2) Serum HSP70levelswere remarkable increased in PCOS patients compared with controls (P <0.001).(3) SerumHSP70concentrations were significantly correlated with serum FPG, FPI, CHO, MDA,CRP, TNF-a, and HOMA-IR.(4) We observed the AUC in model1was0.7952(95%CI0.7062-0.8843), and that in a model with serum HSP70level plus the model1was0.8583(95%CI0.7872-0.9294); P=0.0283for the difference of the AUCs. The establishedconventional model here consists of age, BMI and HOMA-IR.Conclusion: The serum levels of biomarkers (MDA, NO, CRP, and TNF-a) in PCOSpatients were significantly higher than in the controls, which confirmed that oxidativestress and chronic inflammation play an important role in the pathological process in PCOS;While serum HSP70concentrations have a strong positive correlation with the levels of NO,MDA, CRP, TNF-a in PCOS patient, and the association between elevated serum HSP70concentrations and PCOS remained significant. These outcomes indicate that HSP70maybe the potential biomarkers of pathogenesis in PCOS. Part Two Serum25(OH) VD levels and risk of PCOSObjective: To explore the relationship between serum25(OH) VD levels and PCOSin our country and integrate the previous findings and summarize the effect of serum25(OH) VD concentrations associated with susceptibility of PCOS.Methods: The recruitment and diagnosis of study objects are identical with the firstpart. The basic information of population was collected by questionnaire. Serum lipidprofiles, glucose, insulin, Ca, VDBP, and25(OH) VD concentrations were detected. Finally,we used Review Manager5.1for Meta-analysis retrieving all studies matched to the searchterms from PubMed/MEDLINE, EMBASE and ISI Web of Science databases.Results:(1) The individuals with PCOS, compared to non-PCOS controls, had higherlevels of T, LH, INS, GLU, TG, MDA and HOMA-IR; however, PCOS patients had lowerlevels of serum E2, Ca and25(OH) VD.(2) Serum25(OH) VD levels were significantlydecreased in patients with PCOS compared with controls (P <0.001).(3) Serum25(OH)VD concentrations were significantly correlated with HOMA-IR, serum T, E2and FPI.(4)Decreased ORs been observed for PCOS associated with higher level of the serum25(OH)VD concentrations. Individuals with the highest quartile of serum25(OH) VDconcentrations compared with the lowest had a significantly decreased risk for PCOS. Afteradjustment for age and BMI, the adjusted OR was0.28(95%CI0.11-0.71; P for trend<0.005). After adjustment for CHO and TG, the adjusted OR was0.48(95%CI0.15-1.55;P for trend <0.011).(5) A total studies comprising four eligible references with this study,including524cases and319controls, were involved in the final Meta analysis.Conclusion: Low status of serum25(OH) VD concentration was associated withPCOS. Meta-analysis show our conclusion is in contrast with the result of Europe andUnited States, suggesting that there are ethnic differences in the serum25(OH) VDlevels with PCOS risk.