%0 Journal Article
%T Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles
%A Asangla Ao
%A Feride Iffet Sahin
%A Ignatia B. Van den Veyver
%A Jacek Majewski
%A Karine Hovanes
%A Kurosh Rahimi
%A Louise Lapensee
%A Magali Breguet
%A Matthew Osmond
%A Ngoc Minh Phuong Nguyen
%A Philippe Sauthier
%A Radhika Srinivasan
%A Ramesh Reddy
%A Rashmi Bagga
%A Sangeetha Mahadevan
%A Somayyeh Fahiminiya
%A Teruko Taketo
%A Trilochan Sahoo
%A Zhao-Jia Ge
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.10.007
%X 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
%K recurrent hydatidiform moles
%K MEI1
%K TOP6BL
%K REC114
%K recurrent miscarriages
%K male infertility
%K female infertility
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218808/