Transcriptomic Analysis Reveals Differentially Expressed Circular RNAs Associated with Fecundity in the Sheep Hypothalamus with Different FecB Genotypes

Simple Summary This study investigates the expression characteristics of circRNAs during follicular development in sheep with the FecB gene mutation through the use of RNA sequencing. A total of 38,979 circRNAs were identified, and differential expression was observed between different genotypes and developmental stages. Functional enrichment analysis revealed that these differentially expressed circRNAs are associated with signaling pathways such as MAPK, gap junctions, and progesterone-mediated oocyte maturation. This study also predicted a competitive endogenous RNA network, suggesting that specific circRNAs may be involved in regulating LH synthesis and secretion, thereby influencing the process of ovulation. These findings provide important insights into the role of circRNAs in follicular development and ovulation in the sheep hypothalamus and have practical implications for the improvement of sheep breeding practices.Abstract Circular RNAs (circRNAs) are a specific type of noncoding RNA, and some have defined roles in cellular and biological processes. However, little is known about the role of circRNAs in follicular development in sheep with FecB (fecundity Booroola) mutations. Here, the expression profiles of circRNAs were investigated using RNA sequencing (RNA-seq) in the follicular phase (F) and the luteal phase (L) of FecB mutant homozygous (BB) and wild-type (WW) Small Tail Han sheep. A total of 38,979 circRNAs were identified, and 314, 343, 336, and 296 of them were differentially expressed (DE) between BB_F and BB_L, WW_F and WW_L, BB_F and WW_F, and BB_L and WW_L, respectively. The length, type, and chromosome distribution of the circRNAs and the expression characteristic between the circRNAs and their host genes in the sheep hypothalamus were ascertained. Enrichment analysis showed that the host genes of DE circRNAs in the follicular and luteal phases were annotated to MAPK, gap junctions, progesterone-mediated oocyte maturation, oocyte meiosis, and other hormone-related signaling pathways, and the different FecB genotypes were annotated to the gap junctions, circadian entrainment, MAPK, and other hormone-related signaling pathways. The competing endogenous RNA network prediction revealed that the 129 target miRNAs might be bound to 336 DE circRNAs. oar_circ_0000523 and oar_circ_0028984, which were specifically expressed during the follicular phase in the BB genotype sheep, probably acted as miRNA sponges involved in the regulation of LH synthesis and secretion. This study reveals the expression profiles and characterization of circRNAs at two phases of follicular development considering different FecB genotypes, thereby providing an improved understanding of the roles of circRNAs in the sheep hypothalamus and their involvement in follicular development and ovulation.