title: Unique insights into maternal mitochondrial inheritance in mice.
abstract: In animals, mtDNA is always transmitted through the female and this is termed "maternal inheritance." Recently, autophagy was reported to be involved in maternal inheritance by elimination of paternal mitochondria and mtDNA in Caenorhabditis elegans; moreover, by immunofluorescence, P62 and LC3 proteins were also found to colocalize to sperm mitochondria after fertilization in mice. Thus, it has been speculated that autophagy may be an evolutionary conserved mechanism for paternal mitochondrial elimination. However, by using two transgenic mouse strains, one bearing GFP-labeled autophagosomes and the other bearing red fluorescent protein-labeled mitochondria, we demonstrated that autophagy did not participate in the postfertilization elimination of sperm mitochondria in mice. Although P62 and LC3 proteins congregated to sperm mitochondria immediately after fertilization, sperm mitochondria were not engulfed and ultimately degraded in lysosomes until P62 and LC3 proteins disengaged from sperm mitochondria. Instead, sperm mitochondria unevenly distributed in blastomeres during cleavage and persisted in several cells until the morula stages. Furthermore, by using single sperm mtDNA PCR, we observed that most motile sperm that had reached the oviduct for fertilization had eliminated their mtDNA, leaving only vacuolar mitochondria. However, if sperm with remaining mtDNA entered the zygote, mtDNA was not eliminated and could be detected in newborn mice. Based on these results, we conclude that, in mice, maternal inheritance of mtDNA is not an active process of sperm mitochondrial and mtDNA elimination achieved through autophagy in early embryos, but may be a passive process as a result of prefertilization sperm mtDNA elimination and uneven mitochondrial distribution in embryos.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Luo
authors.forename: Zhao-Jia
authors.initials: ZJ
authors.lastname: Ge
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Wang
authors.forename: Zong-Zhe
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Ouyang
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C490981:Gtf2h1 protein, mouse; D008164:Luminescent Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D014157:Transcription Factors; D051758:Transcription Factor TFIIH
keywords: assisted reproductive technologies; mitophagy; paternal inheritance