Genome-Wide Discovery and Characterization of Novel Fecundity-Associated lncRNAs Acting as ceRNAs Reveal Their Regulatory Functions in Sheep Fecundity

Sheep production is vital to the global agricultural economy, particularly for meat and wool. However, fecundity varies significantly among breeds, influenced by a complex interplay of genetic, nutritional, and environmental factors. Long non-coding RNAs (lncRNAs) have been recognized as pivotal regulators in numerous biological processes, including reproduction. This study aimed to identify lncRNAs associated with ovarian function and fecundity in sheep. Utilizing RNA sequencing and advanced bioinformatics, including weighted gene co-expression network analysis (WGCNA), a novel lncRNA, ENSOART00020038447 (lncRNA-OV1), was identified as a key regulator in a ceRNA network that modulates ovarian function. Functional assays in KGN cells demonstrated that lncRNA-OV1 enhances cell proliferation by influencing the expression of pivotal cell cycle genes such as CCNB1. Subcellular localization studies revealed that lncRNA-OV1 is predominantly found in the cytoplasm, implying its role in post-transcriptional regulation. Further in vivo studies in transgenic mice validated the critical role of lncRNA-OV1 in ovarian function and fecundity. Overexpression of lncRNA-OV1 increased litter size, while its knockdown decreased fecundity. Mechanistically, lncRNA-OV1 acts as a ceRNA by sponging miRNAs to modulate the expression of target genes crucial for ovarian function. Our findings shed new light on the molecular mechanisms by which lncRNAs regulate ovarian function and fecundity, highlighting the potential of lncRNAs as targets for enhancing fecundity in sheep and potentially other livestock. Supported by the National Natural Science Foundation of China (No. 31970541). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.