Comparative Transcriptomics Identify Key Pituitary Circular RNAs That Participate in Sheep (Ovis aries) Reproduction

SIMPLE SUMMARY: Booroola fecundity gene (FecB) is known as the main gene for multiple lambs in sheep, which has been shown to affect the reproduction of Small Tail Han sheep. The three genotypes of FecB are BB (two copies of FecB mutation), +B (one copy of FecB mutation), and ++ (without FecB mutation). FecB ++ genotype Small Tail Han sheep usually have one offspring. Interestingly, we found that FecB ++ Small Tail Han sheep also had high-reproductive-capacity individuals (multiple lambs per litter). The pituitary affects reproductive processes of animals through a variety of hormones. How pituitary circular RNAs (circRNAs) affect fecundity in FecB ++ genotype sheep remains unknown. Through RNA sequencing, we speculated that changes in circRNAs may be related to the response of the pituitary to steroid hormones, and directly or indirectly affect the pituitary function and the fecundity of sheep. These results provide new insights into pituitary function and high fecundity in sheep. ABSTRACT: CircRNAs have been found to play key roles in many biological processes and have diverse biological functions. There have been studies on circRNAs in sheep pituitary, and some important circRNAs have been found. But there are still few studies on circRNAs in sheep pituitary with different fecundity. In this study, we obtained the circRNAs expression profiles in the pituitary of FecB ++ genotype Small Tail Han sheep with different fecundity and estrous phases. A total of 34,878 circRNAs were identified in 12 pituitary samples, 300 differentially expressed circRNAs (DE circRNAs) (down: 104; up: 196) were identified in polytocous sheep in the follicular phase (PF) and monotocous sheep in the follicular phase (MF) (PF vs. MF), and 347 DE circRNAs (down: 162; up: 185) were identified in polytocous sheep in the luteal phase (PL) and monotocous sheep in the luteal phase (ML) (PL vs. ML). Cortisol synthesis and secretion pathway (follicular phase) and estrogen signaling pathway (luteal phase) were obtained by functional enrichment analysis of circRNAs source genes. Competing endogenous RNA (ceRNA) network analysis of key DE circRNAs revealed that oar-circ-0022776 (source gene ITPR2, follicular phase) targeted oar-miR-432, oar-circ-0009003 (source gene ITPR1, luteal phase) and oar-circ-0003113 (source gene PLCB1, luteal phase) targeted oar-miR-370-3p. We also explored the coding ability of DE circRNAs. In conclusion, our study shows that changes in the pituitary circRNAs may be related to the response of the pituitary to steroid hormones and regulate the reproductive process of sheep by affecting the pituitary function. Results of this study provide some new information for understanding the functions of circRNAs and the fecundity of FecB ++ genotype sheep.