Liu Lihong, Ha Siyao, Cao Dan, Li MingQing, Li Zhiling
Reproductive Center, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, 515041, China.
Institute Obsterics and Gynecology, Hospital of Obsterics and Gynecology,Fudan University, Shanghai, 200080, China.
Mol Med. 2025 Mar 12;31(1):95. doi: 10.1186/s10020-025-01143-3.
Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage and commonly serves as an indicator of embryonic totipotency. However, its precise role in embryo development remains mysterious. We utilized DRUG-seq to investigate the effects of oxidative damage on genes and TEs expression. Our findings revealed that exposure to hydrogen peroxide (HO) could induce DNA damage, apoptosis, and incomplete DNA demethylation in embryos, which were potentially associated with MERVL expression. To further explore its function, antisense nucleotides (ASO) targeting MERVL were constructed to knockdown the expression in early embryos. Notably, this knockdown led to the occurrence of DNA damage and apoptosis as early as the 2-cell stage, consequently reducing the number of embryos that could progress to the blastocyst stage. Moreover, we discovered that MERVL exerted an influence on the reprogramming of embryonic DNA methylation. In MERVL-deficient embryos, the activity of the DNA demethylase ten-eleven translocation 3 (TET3) was suppressed, resulting in impaired demethylation when compared to normal development. This impairment might underpin the mechanism that impacts embryonic development. Collectively, our study not only verified the crucial role of MERVL in embryonic development but also probed its regulatory function in DNA methylation reprogramming, thereby laying a solid foundation for further investigations into MERVL's role.
转座元件（TEs）约占真核生物基因组的一半，对基因组可塑性有显著贡献。在本研究中，我们聚焦于一种特定的转座元件MERVL，它在二细胞阶段表现出特殊表达，通常作为胚胎全能性的指标。然而，其在胚胎发育中的精确作用仍不清楚。我们利用DRUG-seq研究氧化损伤对基因和转座元件表达的影响。我们的研究结果表明，暴露于过氧化氢（H₂O₂）会诱导胚胎中的DNA损伤、细胞凋亡和不完全DNA去甲基化，这可能与MERVL表达有关。为了进一步探究其功能，构建了靶向MERVL的反义核苷酸（ASO）以敲低早期胚胎中的表达。值得注意的是，这种敲低早在二细胞阶段就导致了DNA损伤和细胞凋亡的发生，从而减少了能够发育到囊胚阶段的胚胎数量。此外，我们发现MERVL对胚胎DNA甲基化重编程有影响。在缺乏MERVL的胚胎中，DNA去甲基化酶十一-易位蛋白3（TET3）的活性受到抑制，与正常发育相比，导致去甲基化受损。这种损伤可能是影响胚胎发育机制的基础。总的来说，我们的研究不仅验证了MERVL在胚胎发育中的关键作用，还探究了其在DNA甲基化重编程中的调控功能，从而为进一步研究MERVL的作用奠定了坚实基础。
