Expression Of BiP And CHOP In Luteal Granulosa Cells Of Follicles From Polycystic Ovary Syndrom

Polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality diseasesoccurring in female of reproductive age. Both ovaries of PCOS patients contain a largenumber of small follicle. However, follicular developmental disorders, they are not ableto produce mature follicle periodically. The mechanism may be related to the selection,development and atresia regulation disorders of the follicle. A large number of studieshave revealed that apoptosis plays an important role during follicular growth develop-ment and apoptosis generated in the egg follicle, oocyte loss/selection and atresia. Inthe fetal period, apoptosis is mainly involved in the oocytes. Apoptosis involving thegranulosa cells of growing follicles in the growth period. Therefore, there may be abnormalregulation of granulosa cell apoptosis in the pathogenesis of PCOS. Moreover, studieshave shown that there are abnormal ovarian granulosa cell apoptosis in PCOS. Endo-plasmic reticulum stress(ER stress) is a pathological state when the physiological func-tions of the endoplasmic reticulum happens disorder. ER stress is the body of aself-defense mechanism. However, apoptotic cell death is induced in the event of pro-longed or severe ER stress. The endoplasmic reticulum-stress-mediated apoptosis path-way is a novel apoptosis pathway in recent years. Cells have evolved various protectivestrategies, collectively termed the unfolded protein response (UPR), to cope with thedetrimental consequences of ER stress. The UPR is thus a pro-survival response thatreduces the accumulation of unfolded or misfolded proteins and restores normal ERfunctioning. However, apoptotic cell death is induced in the event of prolonged or se-vere stress. In recent years, ER stress has a wide range of metabolic syndrome. And Partof the PCOS patients and multiple metabolic abnormalities. But, the relationship of ER stressand PCOS has not been reported. In view of BiP and CHOP are the two signs of the protein of the ER stress. In the present study, we primarily examined whether BiP ex-pression are altered in granulosa cells of ovary in order to investigate ER stress involvedin the underlying pathogenesis of PCOSOBJECTIVE:The purposes of this study were to the expressions of BiP and CHOP in luteal granulosacells of ovary from PCOS. Based on these experiments, we tried to make some explora-tion on the pathogenesis of PCOS.METHODS:We took45cases of ovarian luteal granulosa cells from infertilitas PCOS, PCOS womenwere selected according to Rotterdam Criteria. And45control patients had to fulfill thefollowing selection criteria: healthy female partner in infertile couple, aged<35yearsand regular menstrual cycles luteal granulosa cells of ovary as control group. Diagnosisincluded male factor and tubal factor infertility. The expression of endoplasmic reticu-lum stress protein BiP and CHOP protein was analysed by RT-PCR andWestern-blotting.RESULTS:1. Comparison of clinical indicators of the two groupsThere were no significant differences in age (29.96±4.20), Baseline serum FSH (5.71±1.31VS6.33±1.80), fasting glucose (27±0.44VS5.16±0.45), fertility rate (75.47%VS75.78%) and cleavage rate (96.46%VS96.47%) between PCOS women and controlpatients (P>0.05). However, BMI, LH, androstenedione, testosterone, SHBG, fastinginsulin, HOMA-IR were higher in granulose cells of ovary from PCOS women than fromcontrol patients(P<0.05). Moreover, SHBG were higher in granulose cells of ovaryfrom PCOS women than from control patients(P<0.05). 2． Expression of endoplasmic reticulum stress protein BiP and CHOP mRNA inluteal granulosa cellsLevel of BiP mRNA was significantly higher in luteal granulose cells of ovaryfrom PCOS women than from control patients(1.09±0.63VS0.79±0.34) by RT-PCR(P=0.021). Level of CHOP mRNA was higher in luteal granulose cells of ovary fromPCOS women than from control patients(0.45±0.20VS0.40±0.18), but there were nosignificant differences (P=0.061).3. Expression of endoplasmic reticulum stress protein BiP and CHOP protein inluteal granulosa cellsLevel of BiP protein was significantly higher in luteal granulose cells of ovary fromPCOS women than from control patients(0.56±0.13VS0.40±0.17) by Western blot-ting analysis(P=0.040) and the evel of CHOP protein was higher in luteal granulosecells of ovary from PCOS women than from control patients (0.62±0.26VS0.56±0.17), but there were no significant differences (P=0.261).4． Expression of endoplasmic reticulum stress protein BiP and CHOP mRNA inluteal granulosa cells of PCOSwith IRand non-IRLevel of BiP、CHOP mRNA was significantly higher in luteal granulose cells of PCOSin IRwomen than in non-IR patients ((1.41±0.88VS0.80±0.31),(0.50±0.16VS0.38±0.19)), but there were no significant differences (P<0.05).5. Expression of endoplasmic reticulum stress protein BiP and CHOP protein inluteal granulosa cells of PCOSwith hyperandrogenism and non-hyperandro-genismLevel of BiP、CHOP mRNA was significantly higher in luteal granulose cells of PCOS in hyperandrogenism women than in non-hyperandrogenism patients ((1.28±0.72VS0.77±0.67),(0.49±0.20VS0.34±0.08))(P<0.05).Conclusion:In PCOS, ER stress hallmark protein of abnormal expressed, suggesting that ER stressmay be involved in the pathogenesis of PCOS. This study provides a rationale for fur-ther studies aimed at evaluating any correlation between ER stress and different clini-cal/serological aspects of PCOS.