Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition

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Abstract
The female gamete (the oocyte) serves the distinct purpose of transmitting the maternal genome and other maternal factors that are critical for post-ovulation events1,2,3,4. Through the identification and characterization of oocyte-specific factors, we are beginning to appreciate the diverse functions of oocytes in ovarian folliculogenesis, fertilization and embryogenesis5,6. To understand these processes further, we identified genes called zygote arrest 1 (Zar1 and ZAR1 in mouse and human, respectively) as novel oocyte-specific genes. These encode proteins of 361 amino acids and 424 amino acids, respectively, which share 59% amino-acid identity and an atypical plant homeo-domain (PHD) motif7. Although Zar1-null (Zar1−/−) mice are viable and grossly normal, Zar1−/− females are infertile. Ovarian development and oogenesis through the early stages of fertilization are evidently unimpaired, but most embryos from Zar1−/− females arrest at the one-cell stage. Distinct pronuclei form and DNA replication initiates, but the maternal and paternal genomes remain separate in arrested zygotes. Fewer than 20% of the embryos derived from Zar1−/− females progress to the two-cell stage and show marked reduction in the synthesis of the transcription-requiring complex8, and no embryos develop to the four-cell stage. Thus, Zar1 is the first identified oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition and, as such, offers new insights into the initiation of embryonic development and fertility control in mammals.