Loss of uterine EGR2 contributes to age-associated decline in fertility in female mice.

Early growth response 2 (Egr2) is a pleiotropic zinc finger transcription factor with established roles in neural and immune system, but its uterine function remains poorly understood. We found that uterine EGR2 is expressed in luminal epithelium, glandular epithelium, and stroma of human and mouse uteri, with dynamic regulation across the menstrual cycle and early pregnancy. EGR2 expression declined in aged and Sirt1 -deficient mouse uteri, models of reproductive aging. Conditional uterine deletion of EGR2 caused mild subfertility, with fewer litters and total pups per female. These findings indicate EGR2 supports, but is not essential for, uterine function.