Department of Human Genetics, McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
Department of Human Genetics, McGill University Health Centre, Montréal, QC H4A 3J1, Canada; Genome Québec Innovation Center, Montréal, QC H3A 0G1, Canada.
Am J Hum Genet. 2018 Nov 1;103(5):740-751. doi: 10.1016/j.ajhg.2018.10.007.
Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1 oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.
具有完全性葡萄胎特征的雄激素源性肿瘤是一种人类妊娠，其中没有胚胎，每 1400 次妊娠中就会发生 1 次。它们主要具有雄激素源性单倍体基因组，所有染色体均源自一个单倍体精子，没有母系染色体。雄激素源性完全性葡萄胎肿瘤于 1977 年被描述，但它们的发生机制仍然是一个悬而未决的问题。我们在经常发生雄激素源性完全性葡萄胎肿瘤的女性中鉴定出了 MEI1、TOP6BL/C11orf80 和 REC114 中的双等位有害突变，这些基因在减数分裂双链断裂的形成中发挥作用。我们研究了 Mei1 缺陷型雌性小鼠中雄激素发生的情况，发现它们 8%的卵子通过将纺锤体与染色体一起挤出第一极体而失去所有染色体。我们证明 Mei1 卵子能够受精，其中 5%产生雄激素源性受精卵。因此，我们揭示了哺乳动物减数分裂异常和产生雄激素源性受精卵的机制，即所有母系染色体及其纺锤体被挤出第一极体。
