Nguyen, N.M.P.Ge, Z.-J.Reddy, R.Fahiminiya, S.Sauthier, P.Bagga, R.Sahin, F.I.Mahadevan, S.fOsmond, M.Breguet, M.Rahimi, K.Lapensee, L.Hovanes, K.Srinivasan, R.Van den Veyver, I.B.Sahoo, T.Ao, A.Majewski, J.Taketo, T.Sim, R.2019-06-272019-06-27201800029297https://www.sciencedirect.com/science/article/pii/S0002929718303598?via%3Dihubhttp://hdl.handle.net/11727/3727Androgenetic 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. © 2018 American Society of Human Geneticsenginfo:eu-repo/semantics/openAccessfemale infertilitymale infertilityMEI1REC114recurrent hydatidiform molesrecurrent miscarriagesTOP6BLarticle10357407510004489421000092-s2.0-85055098421