Pharmacological insights into targeting PI3K/Akt and NF-κB pathways for treating endometriosis-associated infertility.

To elucidate the mechanisms of endometriosis-associated infertility and identify potential drug targets by targeting PI3K/Akt and NF-κB signaling pathways. This study assessed clinical characteristics, inflammatory and oxidative stress biomarkers and molecular changes in 300 patients categorized into mild, severe, and control groups. Single-cell RNA sequencing identified potential drug targets, while cell culture and animal models evaluated the effects of pathway inhibitors on endometrial cells and fertility. Endometriosis patients, especially those with severe disease, exhibited higher rates of ovulatory dysfunction, tubal obstruction and impaired endometrial receptivity. Elevated IL-6 and TNF-α levels, reduced SOD activity and increased MDA levels indicated significant inflammation and oxidative stress. Enhanced expression of PI3K/Akt and NF-κB pathways was found in endometriosis tissue. Inhibition of these pathways in vitro and in animal models suppressed endometrial cell growth and invasiveness and increased fertility. This study highlights the roles of PI3K/Akt and NF-κB pathways in endometriosis-associated infertility and provides a basis for developing targeted treatments and improving diagnosis.