[No authors listed]
Human zygote arrest during in vitro culture is rare and the etiology is unclear. The oocyte-specific gene Zar1 plays an essential role in oocyte-embryo transition, and most embryos from Zar1 knockout female mice arrest at the one-cell stage. This study investigates whether maternal ZAR1 gene variations play a role in human zygote arrest. Sequence analysis of ZAR1 was conducted for 47 women with recurrent uncleaved zygotes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (â¥â70% 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) of ZAR1 were identified in the zygote arrest group but not in any of the 188 controls. However, the bioinformatics analysis revealed that neither of the mutations in ZAR1 has 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 (Pâ=â0.047, ORâ=â3.66). Allele frequencies of these two SNPs were also significantly different between the case group and control subset II (Pâ=â0.024, ORâ=â3.28). In conclusion, two SNPs in ZAR1 are associated with human zygote arrest, although additional proof is needed for validation.
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