ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation

Abstract

Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained decreased levels of many maternal mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell-cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3′-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.

Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro

“…Differences in maternal gene expression lead to the lower developmental potential of aged oocytes. For instance, ZAR1 plays essential role in transition from oocyte to embryo 38 , and its expression in this study was found to be reduced in aged oocytes. Furthermore, Ax treatment was helpful to maintain the maternal gene expression for C-MOS , CCNB1 , BMP15 , CDX2 and POU5F1 in aged oocytes.…”

RNA-Seq transcriptome reveals different molecular responses during human and mouse oocyte maturation and fertilization

“…Oocyte maturation and fertilization have been explored for many years [21,33,34]; however, little is known regarding the different mechanisms between human and mouse. Here, we analyzed the transcriptomes of human and mouse GV and MII oocytes to explore the differences between human and mouse oocytes at the transcriptional level [22,35].…”

“…Several studies have explored the mechanisms of maternal mRNA decay in mouse oocytes. For example, BTG4, CNOT6L and ZAR1/2 participate in the destruction of target specific transcripts during oocyte maturation [13,34,36]. However, the differences of selectively degraded transcripts between human and mouse have not been explored in detail.…”

PABPN1L mediates cytoplasmic mRNA decay as a placeholder during the maternal‐to‐zygotic transition

“…Similarly, transcription of MuERV-L target genes, including Guca1a, Tead4, Tdpoz1/4, and Zfp352, was also blocked after maternal Pabpn1l deletion (Appendix Fig S1B). We also microinjected zygotes (WT and Pabpn1l ♀À/♂+ ) with the MuERV-L::tdTomato reporter plasmid (MuERV-L 5 0 -long terminal repeat (LTR) promoters upstream of the red fluorescent protein tdTomato) as previously described [36,38] and monitored the expression of tdTomato during culture. TdTomato expression was observed in WT 2-cell embryos but not in Pabpn1l ♀À/♂+ embryos, which arrested at the 1-to 2-cell stage (Fig 3E and F).…”