Novel Insights into the Regulation of GnRH Secretion in Sheep Hypothalamic Nerve Cells by the GRM1 Gene

Seasonal estrus limits sheep farming efficiency, making enhanced reproductive capacity and year-round estrus crucial for efficient breeding. GRM1 could modulates neuronal signals and stimulates neuron excitability. Our preliminary transcriptomic analysis of hypothalamic tissues from Kazakh ewes during nonbreeding season anestrus and nonbreeding season nutritionally induced estrus strongly suggested that GRM1 is a candidate gene that regulates estrus. The role of GRM1 in sheep estrus remains to be investigated. GRM1 expression was measured in hypothalamic tissues of Kazakh sheep during nonbreeding anestrus and nutritionally induced estrus via qPCR and immunohistochemistry. GRM1’s regulatory role in GnRH secretion and gene expression was studied in hypothalamic neurons via overexpression and RNAi. GnRH secretion changes were quantified by ELISA. GRM1 mRNA expression was significantly increased in the hypothalamus of estrous Kazakh sheep, as confirmed by immunohistochemical staining. The results of hypothalamic neuron experiments revealed that the expression of GRM1 was significantly upregulated after overexpression, which affected the expression of GnAQ, ITPR1, PLCB1 and PRKCB and ultimately promoted the secretion of GnRH. The expression of GnRH decreased after the interference in GRM1 expression. GRM1 modulates the secretion of GnRH in the hypothalamic nerve cells of Kazakh sheep through the glutamatergic synapse–calcium signaling pathway.