Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

SIMPLE SUMMARY: Previous studies revealed that alternative splicing (AS) events and gene variants played key roles in reproduction. However, their location and distribution in hypothalamic fecundity-related genes in sheep without the FecB mutation remain largely unknown. In this study, we performed a correlation analysis of transcriptomics and proteomics, and the results suggested several differentially expressed genes (DEGs)/differentially expressed proteins (DEPs), including galectin 3 (LGALS3), aspartoacylase (ASPA) and transthyretin (TTR), could be candidate genes influencing ovine litter size. Further analysis suggested that AS events, single nucleotide polymorphisms (SNPs) and microRNA (miRNA)-binding sites existed in key DEGs/DEPs, such as ASPA and TTR. This study provides a new insight into ovine and even other mammalian reproduction. ABSTRACT: Previous studies revealed that alternative splicing (AS) events and gene variants played key roles in reproduction; however, their location and distribution in hypothalamic fecundity-related genes in sheep without the FecB mutation remain largely unknown. Therefore, in this study, we described the hypothalamic AS events and variants in differentially expressed genes (DEGs) in Small Tail Han sheep without the FecB mutation at polytocous sheep in the follicular phase vs. monotocous sheep in the follicular phase (PF vs. MF) and polytocous sheep in the luteal phase vs. monotocous sheep in the luteal phase (PL vs. ML) via an RNA-seq study for the first time. We found 39 DEGs with AS events (AS DEGs) in PF vs. MF, while 42 AS DEGs were identified in PL vs. ML. No DEGs with single nucleotide polymorphisms (SNPs) were observed in PF vs. MF, but five were identified in PL vs. ML. We also performed a correlation analysis of transcriptomics and proteomics, and the results suggested several key DEGs/differentially expressed proteins (DEPs), such as galectin 3 (LGALS3) in PF vs. MF and aspartoacylase (ASPA) and transthyretin (TTR) in PL vs. ML, could be candidate genes influencing ovine litter size. In addition, further analyses suggested that AS events, SNPs and miRNA-binding sites existed in key DEGs/DEPs, such as ASPA and TTR. All in all, this study provides a new insight into ovine and even other mammalian reproduction.