Role of Sirt3 in mitochondrial biogenesis and developmental competence of human in vitro matured oocytes.

作者: Hong-Cui Zhao , Ting Ding , Yun Ren , Tian-Jie Li , Rong Li

DOI: 10.1093/HUMREP/DEV345

关键词:

摘要: STUDY QUESTION Does Sirt3 dysfunction result in poor developmental outcomes for human oocytes after vitro maturation (IVM)? SUMMARY ANSWER Inefficient expression induced decreased mitochondrial DNA copy number and biogenesis, therefore impaired the competence of IVM oocytes. WHAT IS KNOWN ALREADY Cytoplasmic immaturity may lead to reduced competence. Mitochondrial results accumulation free radicals leads mutations, protein damage, telomere shortening apoptosis. SIRT3 (in Sirtuin family) has emerged as a fidelity that directs energy generation regulates reactive oxygen species scavenging proteins. DESIGN, SIZE, DURATION In vivo matured metaphase II (IVO-MII) IVM-MII were donated by 324 infertile patients undergoing assisted reproductive technology cycles (12 60 IVO oocytes, 312 403 oocytes). Five each germinal vesicle (GV), groups compared with respect mRNA levels Sirt1-7 mRNA, five samples at stage analysed mRNA. injected transcribed (n = 59) or small interfering RNA (siRNA) 78). mouse, IVM, mRNA-injection siRNA-injection 5 each) abundance Pgc1α (an inducer biogenesis) mRNAs. Human blastocysts 12), 9), 13) 6) used generate embryonic stem cells (ESCs). addition, 587 IVO-MII 1737 from 83 mice collected compare preliminary oocyte data another species. PARTICIPANTS/MATERIALS, SETTING, METHODS was single-cell real-time PCR. Karyotyping embryos performed an array comparative genomic hybridization method, ESCs cytogenetic analysis. The function gene investigated using siRNA injection. Markers identified immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE A retrospective analysis revealed higher spontaneous abortion rate (P < 0.01) decrease high quality embryo versus controlled ovarian stimulation (COS) cycles. biogenesis 0.05) potential blastocyst significantly when inhibited 0.05 group) but could be up-regulated injection Compared group, comparable efficiency can obtained increased mouse zygotes IVF 0.001 MII oocytes) gradually declined until stage. mice, lower observed preimplantation controls, affected accordance human. Therefore similar role LIMITATIONS, REASONS FOR CAUTION couples study had variety different simple complex factors causing infertility. Additional studies larger are required confirm present owing limited study. WIDER IMPLICATIONS FINDINGS To our knowledge, this is first investigating observation help improve clinical application procedure. FUNDING/COMPETING INTERESTS This work supported part National Natural Science Foundation Key Program (31230047), Ministry Technology China Grants (973 program; 2014CB943203), General (31371521 81571400), Beijing Nova (xxjh2015011), Specialized Research Fund Doctoral Higher Education (20120001130008) Young Scholar (31501201). authors have declared no conflict interest exists.

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