ZAR1/ZAR2-mediated maternal mRNA fate control in oocyte maturation and early embryonic development

Abstract Oocyte maturation and early embryonic development following fertilization occur during a phase of restricted transcriptional activity and are highly dependent on the storage, translational activation, and timed clearance of maternal mRNAs. In recent years, zygote arrest 1 (ZAR1) and its homolog zygote arrest 2 (ZAR2) have been recognized as important factors linking the mitochondria-associated ribonucleoprotein domain (MARDO) to the regulation of maternal mRNA fate. Existing studies show that ZAR1 participates in the spatial storage of maternal mRNA through RNA binding and MARDO-associated localization; In addition, studies using Zar1/Zar2 eficient mouse model further suggests that the combined loss of these proteins may affect maternal mRNA stability, poly(A) tail dynamics, translation activation, and B-cell translocation gene 4 (Btg4)-mediated maternal mRNA clearance, thereby leading to abnormal meiosis, defects in spindle assembly, impaired maternal-to-zygotic transition (MZT), and failure of zygotic genome activation (ZGA). However, the link between decreased ZAR1/ZAR2 expression and abnormal epigenetic modifications in aged oocytes, as well as the relationship between human ZAR1 variants and oocyte maturation disorders and preimplantation embryonic developmental arrest, requires further validation through additional functional experiments and clinical genetic evidence. This review focuses on the ZAR1/ZAR2-MARDO-maternal mRNA regulatory axis and summarizes the molecular characteristics of ZAR1 and ZAR2, MARDO-mediated spatial storage of maternal mRNA, maternal mRNA fate regulation, and their potential implications for oocyte maturation, early embryonic development, and female infertility. It also emphasizes the boundaries between different species, experimental models, and levels of evidence to avoid directly extrapolating findings from animal models to human clinical conclusions.