IFI6 regulation of physiological functions in granulosa cells

Reproductive performance is critical for livestock productivity. Ovarian granulosa cells (GCs) play a central role in female reproduction. These cells are involved in follicular development, maturation, and atresia by regulating proliferation, secretion, and apoptosis. Here, we found that interferon alpha inducible protein 6 (IFI6) is highly expressed in estrous gilts compared to anestrous gilts. Functional studies demonstrated that both knockdown and overexpression of IFI6 alters estrogen synthesis, cell proliferation, and apoptosis in granulosa cells. Mechanistically, IFI6 regulates physiological functions via the Phosphoinositide 3-kinase/protein kinase B (PI3K - Akt) signaling pathway. Moreover, the PI3K-Akt signaling pathway activates activator protein 1 (AP - 1). According to ChIP-Atlas data, AP - 1 binding sites are present in the promoters of genes such as CYP19A1, BAX, BCL2, CYCLIN D, and CYCLIN B. Therefore, we propose a model where IFI6 activates the PI3K-Akt pathway, which in turn upregulates AP - 1 to promote estrogen synthesis and cell proliferation while inhibiting apoptosis. These findings identify that IFI6 plays a critical role in the physiological regulation of porcine ovarian granulosa cells. IFI6 could enhance the precision of genomic selection for improving fertility in porcine.