Primate-specific sperm lnc-CLCN7 reveals embryo quality in IVF

Long non-coding RNAs (lncRNAs) are an essential class of regulatory molecules that participate in diverse biological processes. However, whether sperm-derived lncRNAs from infertile men contribute to impaired embryo development during in vitro fertilization (IVF) remains unclear. In this study, we investigate the lncRNA expression profiles in sperm from asthenozoospermic patients with poor embryo development and explore their potential roles in early embryo development. Microarray analyses identify 993 differentially expressed lncRNAs in sperm samples from these patients, including 626 downregulated and 367 upregulated probes. Among them, an antisense transcript, lnc-CLCN7, is validated as the most significantly dysregulated lncRNA in an expanded cohort. In situ hybridization demonstrates that lnc-CLCN7 is localized in spermatogenic cells of primate testes and within the nuclei of HTR-8 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that lnc-CLCN7 is associated with the regulation of ion transport, ion homeostasis and related signaling pathways. Further experiments demonstrate that Lnc-CLCN7 directly binds to the histone modification H3K9me2/3 in HTR-8 cells and that its expression in sperm is modulated by oxidative stress induced by H ₂O ₂ treatment. Additionally, dysregulation of the glycolysis/gluconeogenesis and pyrimidine metabolism pathways in sperm is found to contribute to poor embryo development. Collectively, our findings identify Lnc-CLCN7 as an H3K9me2/3-binding, oxidative stress-responsive lncRNA that may serve as a potential biomarker for predicting poor embryo development in IVF and provide new insights into the molecular mechanisms linking sperm RNA regulation to embryo quality.