title: The importance of mitochondrial metabolic activity and mitochondrial DNA replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence.
abstract: Mitochondrial metabolic capacity and DNA replication have both been shown to affect oocyte quality, but it is unclear which one is more critical. In this study, immature oocytes were treated with FCCP or ddC to independently inhibit the respective mitochondrial metabolic capacity or DNA replication of oocytes during in vitro maturation. To differentiate their roles, we evaluated various parameters related to oocyte maturation (germinal vesicle break down and nuclear maturation), quality (spindle formation, chromosome alignment, and mitochondrial distribution pattern), fertilization capability, and subsequent embryo developmental competence (blastocyst formation and cell number of blastocyst). Inhibition of mitochondrial metabolic capacity with FCCP resulted in a reduced percent of oocytes with nuclear maturation; normal spindle formation and chromosome alignment; evenly distributed mitochondria; and an ability to form blastocysts. Inhibition of mtDNA replication with ddC has no detectable effect on oocyte maturation and mitochondrial distribution, although high-dose ddC increased the percent of oocytes showing abnormal spindle formation and chromosome alignment. ddC did, however, reduce blastocyst formation significantly. Neither FCCP nor ddC exposure had an effect on the rate of fertilization. These findings suggest that the effects associated with lower mitochondrial DNA copy number do not coincide with the effects seen with reduced mitochondrial metabolic activity in oocytes. Inhibiting mitochondrial metabolic activity during oocyte maturation has a negative impact on oocyte maturation and subsequent embryo developmental competence. A reduction in mitochondrial DNA copy number, on the other hand, mainly affects embryonic development potential, but has little effect on oocyte maturation and in vitro fertilization.
authors.affiliation: Reproductive Health Center, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China. dafeng76@126.com
authors.forename: Hongshan
authors.initials: H
authors.lastname: Ge
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Tollner
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Mimi
authors.initials: M
authors.lastname: Dai
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Li
authors.forename: Heqin
authors.initials: H
authors.lastname: Guan
authors.forename: Dan
authors.initials: D
authors.lastname: Shan
authors.forename: Xiuju
authors.initials: X
authors.lastname: Zhang
authors.forename: Jieqiang
authors.initials: J
authors.lastname: Lv
authors.forename: Changjiang
authors.initials: C
authors.lastname: Huang
authors.forename: Qiaoxiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D056915:DNA Copy Number Variations; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics*; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology*; D005260:Female; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D009866:Oogenesis; D016047:Zalcitabine / Q000494:pharmacology
chemical_list: D004272:DNA, Mitochondrial; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D016047:Zalcitabine