Variation Screening of Zygote Arrest 1(ZAR1) in Women with Recurrent Zygote Arrest During IVF/ICSI Programs

Human zygote arrest during in vitro culture is rare and the etiology is unclear. The oocyte-specific geneZar1plays an essential role in oocyte-embryo transition, and most embryos fromZar1knockout female mice arrest at the one-cell stage. This study investigates whether maternalZAR1gene variations play a role in human zygote arrest. Sequence analysis ofZAR1was conducted for 47 women with recurrent uncleaved zygotes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (>= 70% zygotes uncleaved in at least 2 cycles), 93 women from IVF/ICSI cycles with normal uncleaved rate and live birth (control subset I) and 188 women with spontaneous pregnancy and live birth (control subset II). One novel synonymous variation (c.516C>T) and one novel intron variation (c.964-55A>T) ofZAR1were identified in the zygote arrest group but not in any of the 188 controls. However, the bioinformatics analysis revealed that neither of the mutations inZAR1has effect on ZAR1 protein function. Compared with control subset I, the allele frequencies of rare SNPs rs117545505 and rs17609740 were significantly different in patients with zygote arrest (P = 0.047, OR = 3.66). Allele frequencies of these two SNPs were also significantly different between the case group and control subset II (P = 0.024, OR = 3.28). In conclusion, two SNPs inZAR1are associated with human zygote arrest, although additional proof is needed for validation.