Zygotic genome activation (ZGA) is the first transcriptional event following fertilization in mammals. ZGA is a coordinated process of the degradation of maternal mRNA stored in the oocyte and the transcription of new mRNAs from the zygotic genome. [1][2][3] In mice, ZGA can be divided into two stages: minor ZGA, occurring at the one-cell stage and activating a limited number of genes, and major ZGA, occurring during the mid to late 2-cell stage and initiating the comprehensive transcriptional activation of the zygotic genome. 1,3,4 Alternative splicing is a conserved and important regulatory mechanism to increase the diversity of mRNA isoforms, which allows a single gene to generate different proteins exerting sophisticated functions. [5][6][7][8] Common alternative splicing patterns include exon skipping, intron retention, alternative 5 0 splice site, alternative 3 0 splice site (A3SS) and mutually exclusive exons. These mRNA isoforms are derived from identical precursor messenger RNAs but exhibit variations in retained exon regions. Apart from the common patterns, alternative first exons or alternative promoter usage also can yield mRNA isoforms with distinct 5 0 ends via the use of different transcription start sites. [9][10][11][12] The occur-