Premeiotic deletion of Eif2s2 causes oocyte arrest at the early diplotene stage and apoptosis in mice.
Wenjun ZhouBiao LiZhijuan WangShuang LiuWeiyong WangSihui HeYe ChenXiaodan ZhangMeijia ZhangPublished in: Cell proliferation (2024)
Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2), a subunit of the heterotrimeric G protein EIF2, is involved in the initiation of translation. Our findings demonstrate that the depletion of Eif2s2 in premeiotic germ cells causes oocyte arrest at the pachytene and early diplotene stages at 1 day postpartum (dpp) and 5 dpp, respectively, and eventually leads to oocyte apoptosis and failure of primordial follicle formation. Further studies reveal that Eif2s2 deletion downregulates homologous recombination-related and mitochondrial fission-related protein levels, and upregulates the integrated stress response-related proteins and mRNA levels. Consistently, Eif2s2 deletion significantly decreases the expression of dictyate genes and compromises mitochondrial function, characterized by elongated shapes, decreased ATP levels and mtDNA copy number, along with an excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, DNA damage response and proapoptotic protein levels increase, while anti-apoptotic protein levels decrease in Eif2s2-deleted mice. An increase in oocytes with positive cleaved-Caspase-3 and TUNEL signals, alongside reduced Lamin B1 intensity, further indicates oocyte apoptosis. Collectively, Eif2s2 deletion in premeiotic germ cells causes oocyte meiotic arrest at the early diplotene stage by impairing homologous recombination, and eventually leads to oocyte apoptosis mainly through the downregulation of mitochondrial fission-related proteins, ROS accumulation and subsequent DNA damage.
Keyphrases
- cell cycle arrest
- dna damage
- oxidative stress
- cell death
- induced apoptosis
- dna repair
- endoplasmic reticulum stress
- copy number
- reactive oxygen species
- dna damage response
- genome wide
- pi k akt
- mitochondrial dna
- cell cycle
- signaling pathway
- binding protein
- cell proliferation
- single cell
- physical activity
- nitric oxide
- adipose tissue
- long non coding rna
- metabolic syndrome
- gene expression
- protein kinase
- transcription factor
- amino acid
- skeletal muscle
- anti inflammatory