| BackgroundPolycystic ovary syndrome(PCOS)is usual in women of childbearing age and can lead to reproductive endocrine disorders and metabolic abnormalities.It can manifest as hyperandrogenism/signs,polycystic ovary morphology and ovulation disorders,which lead to infertility,obesity,insulin resistance,cardiovascular disease and so on.About 50-70%of anovulatory infertility is related to PCOS.Arrest of development and over recruitment of follicles are common manifestations which result in nondominant follicle production.It has been suggested that the PCOS follicular development arrest may relate to the ovarian granulosa cell apoptosisFat mass and obesity-associated protein(FTO)is encoded by the gene FTO from chromosome 16,localized in the nucleus and widely expresed during various developmental stages of human tissues.It is involved in various life activities of cells,such as proliferation,differentiation,apoptosis and OS,and the occurrence and development of a variety of diseases,such as obesity,T2DM and diseases of heart and blood vessels.OS is related to abnormal mitochondrial function.FTO is expressed in germ cells and early embryos and involved in meiosis,fertilization and embryonic development.Previous studies of our team have proved that granulosa cells in patients with PCOS have high FTO expression,but the regulatory mechanism remains unclear.Therefore,exploring the correlation between FTO expression and mitochondrial function and cell apoptosis in human ovarian granulosa cells,studying the mechanism of FTO regulating apoptosis of granular cells in PCOS,and finding the link between FTO expression in PCOS granulosa cells and the outcome of IVF-ET can provide new diagnosis and treatment for PCOS and ART treatment.Objective1.To explore the correlation between FTO expression and mitochondrial function,apoptosis in PCOS granulosa cells and ⅣF-ET outcome among PCOS patients;2.To study the mechanism of FTO in regulating granulosa cells apoptosis among PCOS patients.Materials and methodsIn this study,a total of 81 patients with tubal infertility or PCOS were included.The expression of FTO and apoptosis-related factors,mitochondrial function and the level of apoptosis in ovarian granulosa cells were detected.siRNA was used to knock down the expression of FTO in KGN cells to explore the regulatory mechanism of FTO on apoptosis.Then we followed up pregnancy outcomes of IVF-ET among enrolled patients,and analyzed the correlation between FTO expression and them.Results1.In normal groups and overweight groups,the expression of FTO(normal weight:1.88±0.13 vs 0.97±0.19;overweight:1.98±0.28 vs 1.49±0.14),the content of intracellular ROS(normal weight:181.23±20.50 vs 162.47±11.31;overweight:198.34±21.92 vs 172.09± 16.40),the abnormal rate of mitochondria morphology(normal weight:18.30±2.28%vs 7.80±1.02%;overweight:21.20±1.81%vs 9.13±1.73%)and the level of apoptosis(normal weight:35.50±3.61%vs 17.39±2.92%;overweight:37.40±2.45%vs 17.69±2.20%)in PCOS granulosa cells were significantly higher than those in the control group(P<0.05);2.In KGN cells,the level of apoptosis rate(6.69±1.10%vs 18.94±2.30%)and the content of intracellular ROS(136.18±19.70 vs 169.30±15.52)decreased significantly(P<0.05),but there was no significant difference in the abnormal rate of mitochondria morphology(P>0.05);3.The expression of FTO mRNA in PCOS ovarian granulosa cells was negatively correlated with MII egg rate(P<0.05).The expression of FTO mRNA and BMI were independent influencing factors of MII egg rate among PCOS patients(the expression of FTO mRNA:β=-0.315,P<0.05;BMI:β=-0.512,P<0.05).Conclusions1.FTO is highly expressed in ovarian granulosa cells of infertile women with PCOS.FTO promotes apoptosis by mediating mitochondrial dysfunction;2.The expression of FTO mRNA is negatively correlated with MⅡ egg rate inⅣF-ET,indicating that FTO may regulate egg maturation among PCOS patients.Our study provides new ideas for diagnosis and treatment of PCOS and ART treatment. |
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