Androgens are required for the male reproductive tissues. However, in many target tissues the regulation of cell type specific responses to androgen action remain poorly understood. Dramatically declined male fertility with low sperm counts and poor semen quality underlines the compelling need of understanding the process of fine-tuning the androgen response in the epididymis where sperm mature. Androgens signal in cells through androgen receptor. Our studies are aimed at revealing novel mechanisms regulating androgen receptor activity in the epididymis. We will focus on other transcription factors working with androgen receptor, epigenetic marks and post-translational modifications of androgen receptor. With this proposal, we will improve our understanding of the mechanisms of androgen signaling in the epididymis that are relevant for male fertility, in order to uncover targets for novel infertility biomarkers and non-hormonal contraceptive modalities.