有害的线粒体 DNA 突变在成熟卵母细胞中很常见。
Deleterious mtDNA mutations are common in mature oocytes.
机构信息
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, Oregon 97239, USA.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA.
出版信息
Biol Reprod. 2020 Mar 13;102(3):607-619. doi: 10.1093/biolre/ioz202.
Heritable mitochondrial DNA (mtDNA) mutations are common, yet only a few recurring pathogenic mtDNA variants account for the majority of known familial cases in humans. Purifying selection in the female germline is thought to be responsible for the elimination of most harmful mtDNA mutations during oogenesis. Here we show that deleterious mtDNA mutations are abundant in ovulated mature mouse oocytes and preimplantation embryos recovered from PolG mutator females but not in their live offspring. This implies that purifying selection acts not in the maternal germline per se, but during post-implantation development. We further show that oocyte mtDNA mutations can be captured and stably maintained in embryonic stem cells and then reintroduced into chimeras, thereby allowing examination of the effects of specific mutations on fetal and postnatal development.
可遗传的线粒体 DNA（mtDNA）突变很常见，但只有少数反复出现的致病性 mtDNA 变体占已知人类家族病例的大多数。人们认为，在女性生殖细胞中存在纯化选择，这有助于在卵母细胞发生过程中消除大多数有害的 mtDNA 突变。在这里，我们发现，在 PolG 突变体雌性产生的已排出的成熟小鼠卵母细胞和着床前胚胎中存在大量有害的 mtDNA 突变，但在其活产后代中不存在。这意味着，纯化选择不是在母系生殖细胞本身起作用，而是在胚胎着床后发育过程中起作用。我们进一步表明，卵母细胞 mtDNA 突变可以在胚胎干细胞中捕获并稳定维持，然后再引入嵌合体中，从而可以检查特定突变对胎儿和产后发育的影响。
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