LINE-1 逆转座子在小鼠胎儿卵母细胞损耗中的作用。
A role for retrotransposon LINE-1 in fetal oocyte attrition in mice.
机构信息
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Dev Cell. 2014 Jun 9;29(5):521-533. doi: 10.1016/j.devcel.2014.04.027. Epub 2014 May 29.
Fetal oocyte attrition (FOA) is a conserved but poorly understood process of elimination of more than two-thirds of meiotic prophase I (MPI) oocytes before birth. We now implicate retrotransposons LINE-1 (L1), activated during epigenetic reprogramming of the embryonic germline, in FOA in mice. We show that wild-type fetal oocytes possess differential nuclear levels of L1ORF1p, an L1-encoded protein essential for L1 ribonucleoprotein particle (L1RNP) formation and L1 retrotransposition. We demonstrate that experimental elevation of L1 expression correlates with increased MPI defects, FOA, oocyte aneuploidy, and embryonic lethality. Conversely, reverse transcriptase (RT) inhibitor AZT has a profound effect on the FOA dynamics and meiotic recombination, and it implicates an RT-dependent trigger in oocyte elimination in early MPI. We propose that FOA serves to select oocytes with limited L1 activity that are therefore best suited for the next generation.
胎儿卵母细胞耗竭（FOA）是一个保守但尚未被充分理解的过程，即在出生前，超过三分之二的减数分裂前期 I（MPI）卵母细胞被淘汰。我们现在发现，逆转录转座子 LINE-1（L1）在胚胎生殖细胞的表观遗传重编程过程中被激活，参与了小鼠的 FOA。我们表明，野生型胎儿卵母细胞具有不同的 L1ORF1p 核水平，L1ORF1p 是 L1 编码蛋白，对于 L1 核糖核蛋白颗粒（L1RNP）的形成和 L1 逆转录至关重要。我们证明，实验性提高 L1 表达与 MPI 缺陷、FOA、卵母细胞非整倍体和胚胎致死率增加相关。相反，逆转录酶抑制剂 AZT 对 FOA 动力学和减数分裂重组有深远影响，它暗示在早期 MPI 中，卵母细胞消除有一个依赖 RT 的触发因素。我们提出，FOA 有助于选择 L1 活性有限的卵母细胞，这些卵母细胞最适合下一代。
Zotero 插件