Integrated multi-omics analysis reveals molecular regulation of the hypothalamus-pituitary-ovary axis underlying egg...

This study was conducted to systematically elucidate the molecular regulatory mechanisms underlying egg production traits in indigenous chickens. Using a self-bred White-feathered Green-shelled (WG) chicken line as the research subject, high-yield and low-yield individuals were selected based on egg numbers at 43 weeks (EN43). Hypothalamus, pituitary, and ovarian tissues were collected from these individuals for targeted metabolomics profiling and transcriptome sequencing. The results showed a significant difference in EN43 between the two groups (P < 0.05). Targeted metabolomics of ovarian tissue detected a total of 17 steroid hormones, among which pregnenolone, progesterone, and 17β-estradiol were identified as differentially expressed steroid hormones (DESHs) between the two groups. Differential expression analysis of transcriptomes identified 666, 149, and 69 differentially expressed genes (DEGs) in the hypothalamus, pituitary, and ovary, respectively. Functional enrichment analysis revealed that hypothalamic DEGs were primarily involved in transcriptional regulation, neuropeptide signaling, and neurodevelopmental processes. Pituitary DEGs were mainly enriched in synaptic plasticity, calcium ion binding, and neurotransmitter transport, while ovarian DEGs were predominantly associated with signal transduction, calcium signaling regulation, and the cGMP signaling pathway. A molecular regulatory network (MRN) was constructed based on DEGs and DESHs. Through modular analysis, four key regulatory modules were identified, involving neuroendocrine regulation, neurotransmitter transport, steroid hormone synthesis, and transcriptional/developmental regulation. Combined with comprehensive network topology scoring, 25 potential candidate genes were identified, including POMC, NPY, CRH, SLC18A2, CD36, EGF, and WNT3A. In conclusion, this study integrated multi-omics data to reveal the molecular mechanisms of the HPO axis regulating egg production traits from a multi-tissue and multi-level perspective, providing a theoretical foundation for molecular breeding in indigenous poultry.