Synaptotagmin-1 regulates egg production by con trolling luteinizing hormone secretion in chickens

Egg production represents one of the most economically critical traits in commercial poultry production, orchestrated primarily by the hypothalamus-pituitary-ovarian (HPO) axis. Synaptotagmin 1 (SYT1), a ubiquitous component of the nervous and endocrine systems, functions as a key mediator of calcium-dependent neurotransmitter release and hormone secretion. However, the functional role of SYT1 in avian reproductive performance has remained elusive. In this study, we present evidence that single nucleotide polymorphisms (SNPs) within the SYT1 gene effectively distinguish commercial laying hens from local wild breeds, as demonstrated through principal component analysis (PCA), suggesting the gene's pivotal role in selective breeding for enhanced egg production. Through genotype-phenotype correlation analyses, we identified two SNPs, rs39497549 and rs39477032, that exhibit strong associations with egg laying performance. Furthermore, tissue-specific expression levels showed profiling analysis revealed SYT1 transcript levels in pituitary and ovarian tissues of high-producing hens relative to their low-producing counterparts, and these expression levels showed strong positive correlations with circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). In addition, fluorescence in situ hybridization analyses further confirmed spatial co-localization of SYT1 and LH within anterior pituitary cells, suggesting a direct involvement of SYT1 in gonadotroph activity. Functional validation through in cultured pituitary cells revealed that gonadotropin-releasing hormone (GnRH) agonist stimulation significantly upregulated SYT1, follicle stimulating hormone beta subunit (FSHβ), and luteinizing hormone beta subunit (LHβ) mRNA, along with enhanced secretion of FSH and LH. Conversely, SYT1 knockdown attenuated GnRH-induced expression and secretion of gonadotropins, while SYT1 overexpression potentiated these effects. Additionally, SYT1 modulated steroidogenesis in ovarian granulosa cells by regulating the expression of steroidogenic enzymes and progesterone production. Taken together, our findings establish SYT1 as a master regulator of chicken egg production performance via modulation of reproductive hormone synthesis and secretion within the HPO axis. These results position SYT1 polymorphisms as promising genetic markers for selective breeding programs in commercial laying hens improving egg production traits in indigenous chicken breeds.