Lysine-specific demethylase 1 (LSD1) participate in porcine early embryonic development by regulating cell autophagy and apoptosis through the mTOR signaling pathway

• Published in: Theriogenology Vol. 224; pp. 119 - 133
• Main Authors: Qi, Jiajia, Zhang, Shaoxuan, Qu, Hexuan, Wang, Yanqiu, Dong, Yanwei, Wei, Huakai, Wang, Yu, Sun, Boxing, Jiang, Hao, Zhang, Jiabao, Liang, Shuang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Autophagy; LSD1; Porcine early embryonic development; Porcine early embryonic development; Autophagy; LSD1
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2024.05.010

Lysine-specific demethylase 1 (LSD1) stands as the pioneering histone demethylase uncovered, proficient in demethylating H3K4me1/2 and H3K9me1/2, thereby governing transcription and participating in cell apoptosis, proliferation, or differentiation. Nevertheless, the complete understanding of LSD1 during porcine early embryonic development and the underlying molecular mechanism remains unclear. Thus, we investigated the mechanism by which LSD1 plays a regulatory role in porcine early embryos. This study revealed that LSD1 inhibition resulted in parthenogenetic activation (PA) and in vitro fertilization (IVF) embryo arrested the development, and decreased blastocyst quality. Meanwhile, H3K4me1/2 and H3K9me1/2 methylase activity was increased at the 4-cell embryo stage. RNA-seq results revealed that autophagy related biological processes were highly enriched through GO and KEGG pathway analyses when LSD1 inhibition. Further studies showed that LSD1 depletion in porcine early embryos resulted in low mTOR and p-mTOR levels and high autophagy and apoptosis levels. The LSD1 deletion-induced increases in autophagy and apoptosis could be reversed by addition of mTOR activators. We further demonstrated that LSD1 inhibition induced mitochondrial dysfunction and mitophagy. In summary, our research results indicate that LSD1 may regulate autophagy and apoptosis through the mTOR pathway and affect early embryonic development of pigs. •LSD1 is distributed in nucleus and dynamically expressed during porcine early embryonic development.•Inhibition of LSD1 reduces porcine early embryonic development ability, upregulates the methylation modification levels of H3K4me1/2 and H3K9me1/2, inducing DNA damage, apoptosis and mitochondrial dysfunction.•LSD1 participates in the development of porcine early embryos by regulating autophagy and apoptosis via mTOR signal pathway.