LPS-induced TLR4 activation enhances NF-κB signalling in human ovarian granulosa-like tumor cell line and induced primordial Follicle activation in mouse ex vivo ovary assay.

The immune system is increasingly recognized as a regulator of ovarian function, yet its role in early folliculogenesis remains unclear. Ovulation exhibits inflammatory-like processes involving Toll-like receptors, which is expressed in early follicles and may influence their activation. This study aims to demonstrate how the TLR4 inhibitor C34 reduces primordial follicle activation in an ex vivo ovary assay. We further examine how this effect relates to LPS stimulation and its interaction with the well-known primordial follicle activation pathway, the AKT signaling pathway. Using Western blotting, we observe increased phosphorylation of AKT. In KGN cells, LPC-induced TLR4 activation triggers NF-κB signalling and ELISA reveals production of the monocyte chemoattractant protein 1 (MCP-1). MCP-1 enhances AKT phosphorylation and cell proliferation, suggesting a link between immune signalling and follicle activation. These findings indicate that LPS-induced activation of TLR4 may interact with PI3K-AKT signalling to regulate primordial follicle activation and ovarian reserve maintenance.