| Primordial follicles raised from the primordial follicles library started development. After primary, secondary follicles gradually develops into antral follicles, antral follicles are more sensitive to gonadotropin began to accelerate growth and form of dominant follicle. The fate of the dominant follicles is ovulation or atresia. The concentration of estrogen reduce within the follicle can not cause the LH peak have a great relationship with dominant follicle atresia, and granulosa cells apoptosis is also a potential mechanism of follicular atresia. Long time, people have done a lot of research work on the follicular atresia, but the molecular mechanism of regulation of follicular atresia is not entirely clear, still need further research and exploration. Clarify the molecular mechanism of this physiological process has a very important significance for improving animal fertility, reproductive diseases, treatment of animal ovulation disorders.The papers selected mice as experimental animals, studies FSH regulation of delayed ovulation dominant follicle atresia and estrogen metabolism genes Cyplbl molecular mechanisms. Conducted a study of the following aspects:(1) Detection the function of FSH on granulosa cell apoptosis in delayed ovulation dominant follicle and related apoptosis genes.(2) Detection of the delayed ovulation dominant follicle estrogen synthesis and metabolism gene expression.(1) Detection of FSH impact on granulosa cell apoptosis and related genes of delayeded ovulation dominant follicles.(2) Detection the expression estrogen metabolism-related genes of the delayeded ovulation follicles.(3) FSH regulated estrogen metabolism key gene Cyplbl expression and estrogen metabolite4-hydroxy-estradiol effect on the granulosa cells.(4) The transcription factor analysis of Cyp1b1promoter region.(5) The role of FSH on Cyplbl transcription factor Statl.(6) FSH regulation of Statl phosphorylation level mechanism. Comprehensive results of this thesis, the following conclusions:(1) FSH suppression delayeded ovulation dominant follicle atresia by inhibiting apoptosis of granulosa cellsGranulosa cell apoptosis is one of the main cause of mouse follicular atresia, we found that FSH can inhibit granulosa cell apoptosis and apoptosis-related genes expressios, such as Caspase-3,9, BIM to rescue delayeded ovulation dominant follicle atresia.(2) FSH suppression granulosa cell estrogen metabolism genes Cyplbl expressionThe study found that the crucial gene of delayed ovulation dominant follicle granulosa cells estrogen metabolism is Cyplbl. The genes Cyplal, Cypla2, Cyp3a in granulosa cells almost no expression. FSH can inhibit Cyplbl expression in granulosa cells in vitro and in vivo, estrogen metabolite4-hydroxy-estradiol (≧10μM) by Cyplbl has a significant effect on cultured granulosa cells apoptosis.(3) FSH regulation of Statl phosphorylation levels of regulation of Cyplbl expressionSite prediction and experimental analysis found that Statl is one of the important transcription factors of Cyp1b1. Chromatin immunoprecipitation analysis showed that FSH may through the transcription factor Statl in Cyplbl promoter region play a regulatory role. Further studies showed that levels of Statl protein is not a significant regulatory by FSH. Statl tyrosine701phosphorylation is not detected in the granulosa cells, but FSH could via p38MAPK activate ser, thr phosphatase PP2A activities lead dephosphorylation of Statl on ser727, and drop from the promoter region of Cyp1b1to regulate expression of estrogen metabolism-related gene Cyplbl in follicle granulosa cells.FSH suppression delayed ovulation follicles atresia and estrogen metabolism, physiological and biochemical studies to determine FSH suppression follicular atresia by inhibiting apoptosis of granulosa cells. Elucidate the molecular mechanism of FSH regulation of follicular estrogen metabolism gene Cyplbl. Help to further elucidate the molecular mechanism of follicular atresia. |
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