| abstract | 第5-7页 |
| 摘要 | 第8-11页 |
| Abbreviation | 第11-12页 |
| Chapter 1 A Brief Review of Ovary development and Metabolism | 第12-55页 |
| Introduction | 第12-45页 |
| 1.1 Ovarian Development and Differentiation | 第13-17页 |
| 1.2 Ovarian Folliculogenesis | 第17-40页 |
| 1.3 CRISPR/Cas9 system for genome engineering | 第40-44页 |
| 1.4 A brief Introduction of Candidate Tumor Suppressor Genes | 第44-45页 |
| References | 第45-55页 |
| Chapter 2 Generation of loss-of-tumor suppressor gene collections in human GCT-derived KGN cells | 第55-76页 |
| Introduction | 第55-57页 |
| Methods and Materials | 第57-59页 |
| Results | 第59-70页 |
| 2.1 Design of paired sgRNAs | 第59-60页 |
| 2.2 Generation of EGFP expressing KGN cell lines and evaluation of CRISPR/Cas9 efficacy | 第60-62页 |
| 2.3 Generation of loss-of-tumor suppressor gene collections in KGN cells | 第62-70页 |
| Discussion | 第70-73页 |
| References | 第73-76页 |
| Chapter 3 Screening for loss-of-tumor suppressor gene-induced mitochondrial biogenesis or impairment inKGN cells | 第76-92页 |
| Introduction | 第76-78页 |
| Methods and materials | 第78-79页 |
| Results | 第79-86页 |
| 3.1 Optimization of cell density and the concentration of compounds | 第79-81页 |
| 3.2 OXPHOS changes after genes loss of function | 第81-84页 |
| 3.3 Further analysis of glycolysis capacity after genes loss-of function | 第84-86页 |
| Discussion | 第86-87页 |
| References | 第87-92页 |
| Chapter 4 Generate Hbp1 genetically engineered mice to verify increased mitochondrial biogenesis in vivo | 第92-107页 |
| Introduction | 第92-93页 |
| Methods and Material | 第93-96页 |
| Results | 第96-102页 |
| 4.1 Generation of Hbp1 genetically engineered mice | 第96-98页 |
| 4.2 Mitochondrial oxidative phosphorylation was improved with Hbp1 deletion in ovary,and HBP1 functions as a negative regulator for OXPHOS in ovarian granulosa cells | 第98-100页 |
| 4.3 Mitochondrial biogenesis increased in Hbp1 null granulosa cells | 第100-102页 |
| Discussion | 第102-104页 |
| References | 第104-107页 |
| Chapter 5 Hbp1 deletion increased follicle numbers and ova rian reserve in mice | 第107-121页 |
| Introduction | 第107-109页 |
| Methods and materials | 第109-110页 |
| Results | 第110-115页 |
| 5.1 Hbp1 deficiency in granulosa cells resulted in increased follicle in mouse ovaries | 第110-112页 |
| 5.2 Hbp1 deletion in oocytes didn't influence follicle activation and follicle development at every stage | 第112-113页 |
| 5.3 Evaluation of oocyte maturation and competence to be fertilized | 第113-115页 |
| Discussion | 第115-118页 |
| References | 第118-121页 |
| Chapter 6 Deletion of Hbp1 led to decreased GCs apoptosis and improvement of follicle reserve | 第121-140页 |
| Introduction | 第121-122页 |
| Methods and materials | 第122-124页 |
| Results | 第124-133页 |
| 6.1 Hbp1 deficiency resulted in decreased apoptosis of GCs and follicle ovarian atresia | 第124-127页 |
| 6.2 Expression of genes,which are involved in hormone response increased with HBP1 deletion | 第127-128页 |
| 6.3 Increased profile of primordial dormancy,co-operation and reduced apoptosis in Hbp1~(-/-) adult ovaries | 第128-130页 |
| 6.4 Ovarian reserve retention is increased in Hbp1~(-/-)mice | 第130-132页 |
| 6.5 Apoptosis and follicle atresia increased when up-regulate HBP1 in mice ovaries,as well the reduced growing follicles | 第132-133页 |
| Discussion | 第133-137页 |
| References | 第137-140页 |
| Acknowledgements | 第140-141页 |
| Publications | 第141-144页 |
