Formation mechanism of agar-like zona pellucida and its adverse effects on human oocytes

Agar-like zona pellucida (ZP) is a type of ZP abnormality that adversely affects oocyte maturation, fertilization, and developmental potential. However, the mechanisms underlying its formation and its detrimental effects on oocytes remain elusive. Through comprehensive analyses including whole-exome sequencing, transcriptome sequencing, Q-PCR, scanning electron microscopy, and transmission electron microscopy, our study found that the c.2785G>C mutation in ATRX may represent a genetic factor contributing to the agar-like ZP formation. Moreover, while mutations in ZP1-4 genes were not essential for agar-like ZP formation per se, an increased proportion of ZP1 protein among the four ZP proteins contributed to this phenomenon. Additionally, up-regulation of PMP22 may also be implicated in agar-like ZP formation and exert deleterious effects on oocyte development. Our findings enhance our understanding of agar-like ZP and provide a theoretical foundation for its treatment in assisted reproduction. Furthermore, our study demonstrates potential applications in contraception as the agar-like ZP effectively inhibits conventional fertilization of oocytes.