Abstract
Litter size is a considerable quality that determines the production efficiency of mutton sheep. Therefore, revealing the molecular regulation of high and low fertility may aid the breeding process to develop new varieties of mutton sheep. CircRNAs are the important factors regulating follicular development, but their mechanism role in the regulation of litter size in Hanper sheep is not clear. In the present study, ovarian tissues from the follicular (F) or luteal phase (L) of Hanper sheep that were either consecutive monotocous (M) or polytocous were collected. Then, we performed transcriptome sequencing to screen for differentially expressed circRNAs (DE-circRNAs) and elucidate their function. In total, 4256 circRNA derived from 2184 host genes were identified in which 183 (146 were upregulated, while 37 were downregulated) were differentially expressed in monotocous sheep in the follicular phase versus polytocous sheep in the follicular phase (MF vs. PF). Moreover, 34 circRNAs (14 were upregulated, while 20 were downregulated) were differentially expressed in monotocous sheep in the luteal phase versus polytocous sheep in the luteal sheep (ML vs. PL). This was achieved through DE-circRNAs function enrichment annotation analysis by GESA, GO, and KEGG, which function through the EGF-EGFR-RAS-JNK, TGF-β and thyroid hormone signaling pathway to affect the litter size of Hanper sheep in MF vs. PF and ML vs. PL. STEM results showed that MAPK signaling pathways play a key role in MF vs. PF and ML vs. PL. Through WGCNA analysis, AKT3 was a core gene in MF vs. PF and ML vs. PL. Moreover, competitive endogenous RNA (ceRNA) network analysis revealed the target binding sites for miRNA such as oar-miR-27a, oar-miR-16b, oar-miR-200a/b/c, oar-miR-181a, oar-miR-10a/b, and oar-miR-432 in the identified DE-cirRNAs.