Abstract

Nerve growth factor (NGF) plays a critical role in reproduction through paracrine and endocrine mechanisms. However, its autocrine effects on uterine receptivity and inflammatory pathways remain unknown. This study is the first to demonstrate NGF’s direct autocrine action on sheep endometrial luminal epithelial cells (SELECs), primary cultures treated with NGF for 12, 24, and 48 h, with or without the NTRK1 antagonist. NGF significantly increased PGE2 (p < 0.0001) and PGF2α (p < 0.0001) levels only at 12 h, with no significant changes at 24 and 48 h. NGF also upregulated the expression of NGF, COX2, and NTRK1 (p < 0.0001), and p75NTR and STAR (p < 0.001), at 12 h, with the effects reversed by NTRK1 inhibition, while no significant changes were observed for TLR4 (p > 0.05). Western blot (WB) analysis was performed exclusively to confirm the presence of NGF protein, revealing no significant differences (p > 0.05) across experimental conditions. These findings highlight NGF’s role in directly regulating SELEC activity through autocrine mechanisms, emphasizing its importance in uterine receptivity and reproductive readiness. This study provides novel insights into NGF’s role in sheep reproduction and its potential applications in fertility treatments. © 2025 by the authors.