Jason D Kofinas, Michelle L Seth-Smith, Yael Kramer, Jessie Van Daele, David McCulloh, Fang Wang, Jamie Grifo, David Keefe
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引用次数: 0
Abstract
Purpose: Induction of meiotic competence is a major goal of the controlled ovarian stimulation used in ART. Do factors intrinsic to the oocyte contribute to oocyte maturation? Deletions in mtDNA accumulate in long-lived post mitotic tissues and are found in human oocytes. If oogenesis cleanses the germline of deleterious deletions in mtDNA, meiotically competent oocytes should contain lower levels of mtDNA deletions vs. meiotically arrested oocytes. We tested this hypothesis using a novel PCR assay for a deletion ratio in human oocytes derived from IVF.
Methods: A real-time PCR assay was developed to measure total mtDNA copy number (mtDNACN) and mtDNA harboring the 5 Kb "common deletion" to enable calculation of the mtDNA deletion ratio (mtDNADR) in 143 cultured oocytes. Kruskal-Wallis test was carried out to compare the total mtDNACN and the mtDNADR among oocytes which matured to metaphase II (MII) vs. oocytes arrested at GV or metaphase I (MI).
Results: 51.75% of oocytes reached MII, and 17% remained at MI. Mean mtDNADR in GV, MI and MII oocytes were 27.87%, 31.88% and 20.05%, respectively. The difference in deletion ratios between GV and MII and between MI and MII stages was statistically significant p < 0.001 and p = 0.034, respectively. Additionally, patient age was found to be positively correlated with time to Polar body extrusion (- 0.278 Pearson correlation).
Conclusions: Oocytes with impaired meiotic maturation contain an increased load of mtDNA deletions. This is the first report of an association between the mtDNA deletion ratio and human oocyte maturation in vitro.
期刊介绍：
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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