Integrated Whole-Transcriptome Analysis to Elucidate the Core Regulatory Network of circRNA Involved in Ovarian...

Area of Science:

• Animal Genomics
• Reproductive Biology
• Molecular Endocrinology

Background:

• Ovarian development and reproductive capacity in sheep are influenced by complex regulatory networks.
• Understanding these networks is crucial for improving ovine reproductive efficiency, particularly in breeds with divergent fecundity.

Purpose of the Study:

• To systematically identify candidate genes and regulatory networks governing ovarian development in sheep breeds with differing fecundity.
• To elucidate the mechanism by which multilevel regulatory networks determine ewe reproductive capacity.

Main Methods:

• Whole-transcriptome sequencing of ovaries from low-fecundity (Ujumqin) and high-fecundity (small-tailed Han) sheep breeds.
• Construction and bioinformatic analysis of competing endogenous RNA (ceRNA) regulatory networks.
• Validation of key circRNA-miRNA-mRNA interactions using dual-luciferase reporter gene assays and qRT-PCR.

Main Results:

• Two distinct ceRNA networks were constructed based on fecundity and ovarian developmental stages.
• Key signaling pathways, including MAPK, JAK-STAT, WNT, Ras, and Hippo, were identified.
• A core regulatory axis, circRNA2058-miR-9226-5p-MET, was pinpointed and validated as a central regulator of ovarian function.

Conclusions:

• The study deciphers a synergistic regulatory network controlling ovine ovarian development.
• The circRNA2058-miR-9226-5p-MET ceRNA axis is identified as a critical molecular switch for follicular dominance in sheep.
• This discovery provides a molecular basis for enhancing ovine reproductive efficiency.