The eukaryotic translation initiation factor 4E (EIF4E) protein family exists widely in eukaryotes, with five isoforms in plants, eight isoforms in Drosophila, one isoform in Saccharomyces cerevisiae, and two isoforms in Schizozoite yeast, zebrafish, and Xenopus [[1], [2], [3], [4], [5]]. The EIF4E protein family has three members that are prevalent in mammals: EIF4E1 (EIF4E or EIF4E1A), EIF4E2 (4EHP or 4E-LP) and EIF4E3 [4]. Recently, a new EIF4E family member, EIF4E1B, which is a similar homolog of EIF4E1A (EIF4E1), has been identified [6]. EIF4E1B is an evolutionarily conserved protein that was copied from the ancestral EIF4E locus in Tetrapoda [7,8].

EIF4E1, EIF4E2, and EIF4E3 in the mammalian EIF4E protein family are homologous, whereas EIF4E1B is a homolog of EIF4E1A/EIF4E1 [5,9,10]. EIF4E1, EIF4E2, and EIF4E3 are expressed in vertebrates [10,11], and EIF4E1B is only specifically expressed in the oocytes and embryos of mice [7,9]. EIF4E is also known as a cap-binding protein. During protein translation initiation, EIF4E interacts with the 5′ m7GppN cap structure of mRNAs and binds to the scaffold protein EIF4G, which plays a binding role. EIF4G and EIF4A combine to form the EIF4F complex. After binding with EIF3, the mRNA can be bound to the ribosome protein 40S to initiate the translation process [12]. EIF4E is a key factor in initiating and regulating protein translation in eukaryotic cells. The activity of EIF4E is regulated by two signaling pathways, PI3K/mTOR/AKT and MAPK/MNK [[13], [14], [15]]. After its activation, EIF4E has multiple functions, such as regulating cell proliferation, differentiation, stress, and the inflammatory response; mediating growth factor signal transduction; and regulating transcription [13,[16], [17], [18]].

Recent studies have shown that members of the EIF4E protein family play important roles in animal reproductive development, primarily through EIF4E binding to the 5′ m7GppN cap structure of mRNAs [19]. In Drosophila embryos, deletion of eIF4E1 leads to apoptosis of embryonic cells [4]. In mouse oocytes, the EIF4E2 protein can interact with the homeobox protein PREP1 to jointly inhibit the translation of Hoxb4 mRNA, leading to the failure of mouse oocyte development [20]. In early Xenopus laevis oocytes, the EIF4E1B and EIF4E-binding proteins 4E-T, Xp54/DDX6 RNA helicases, the RNA-binding proteins PAT and LSM14, and CPEB, which recognizes the 3′UTR of mRNAs, form a CPEB‒mRNP cyclic repressor complex to inhibit translation [11]. Researchers have shown that the use of antisense oligonucleotides (MOs) to knock down eIF4E1b in Xenopus oocytes or inactivation of the EIF4E1B protein by microinjection of specific antibodies can accelerate oocyte maturation, indicating that inactivation of the EIF4E1B protein can destroy the CPEB-mRNP inhibitory translation complex and accelerate the translation process. Ultimately, it accelerates oocyte maturation [7], [11]. Recent studies have demonstrated that EIF4E1B plays a pivotal role in regulating maternal mRNA translation in zebrafish and mice [21,22]. In mouse oocytes, EIF4E1B specifically binds to transcripts encoding translation machinery proteins, chromatin remodelers, and reprogramming factors, thereby promoting their translation in zygotes and protecting them from degradation [22]. It was further discovered that EIF4E1B has the function of selective translational activation of mRNA in mammalian oocytes, enabling EIF4E1B to control the transition from oocyte to embryo by selectively translating maternal mRNA [23]. These findings collectively demonstrate that EIF4E1B orchestrates a sophisticated regulatory mechanism during the mammalian oocyte-to-embryo transition, coordinating maternal mRNA translation with chromatin remodeling to ensure precise developmental progression. Therefore, we hypothesized that EIF4E1B regulated the mammalian oocyte-to-embryo transition by forming a molecular complex with its interacting proteins to regulate mRNA translation, ultimately ensuring oocyte maturation and early embryonic development.

In this study, we used mouse models to investigate the expression and localization of EIF4E1B and its function in oocyte maturation and early embryonic development. The novel step of characterizing the effects of EIF4E1B on oocyte maturation and blastocyst development and the interaction of EIF4E1B with the PPP2CA and HSPA1A proteins indicated the likely involvement of the complex formed by the EIF4E1B, PPP2CA and HSPA1A proteins in the regulation of mouse oocyte maturation and early embryonic development.