Transcriptomic regulation of the hypothalamic-pituitary axis by GnRH immunization in Xizang sheep

Xizang sheep are vital economic livestock in plateau regions. Traditional surgical castration often induces stress and infection. Although immunization presents an alternative method, the physiological mechanisms underlying its effects in Xizang sheep remain unclear. Therefore, this study integrated serum immune-antioxidant indicators with hypothalamus-pituitary transcriptomics to investigate molecular mechanisms of GnRH immunization. Results indicated that serum IgA, IgG, IgM, SOD, and GSH in the immunization (IM) group were significantly higher than in control (CON) and surgical castration (SN) groups, while IL-6 and TNF-α were significantly reduced (<i>p</i> < 0.05). RNA-seq analysis revealed that hypothalamic <i>CYTB</i>, <i>ATP6</i>, <i>COX</i>, <i>ABLIM1</i>, and <i>ABI3</i> were significantly upregulated in IM group, whereas <i>SHISA7</i> and <i>PTPRO</i> were significantly downregulated, with notable enrichment in prion disease, oxidative phosphorylation, and thermogenesis pathways. Pituitary <i>RPL15</i> was upregulated while <i>RPL10A</i>, <i>CACNA1D</i>, <i>ANK1</i>, <i>DDX3X</i>, and <i>KCNMA1</i> were significantly downregulated, showing enrichment in myofibril, contractile fiber, sarcomere, and cytosolic ribosome pathways. Association analysis revealed significant positive correlations between IgG and pituitary <i>ATP6</i>, <i>CYTB</i>, <i>TNNI2</i>, as well as hypothalamic <i>COX1</i>, <i>COX</i>, and <i>ND4</i>. In summary, GnRH immunization outperforms surgical castration by modulating hypothalamic-pituitary genes and enhancing immunity and antioxidants in plateau Xizang sheep, achieving integrated neuroendocrine-immune regulation for healthy husbandry of plateau Xizang sheep.