Postnatal Bimodal Dynamics and Androgen-Induced Masculinization of the External Genitalia in Mice

The corpus cavernosum, a key erectile structure within the penis, plays a central role in male reproductive function. While its prenatal development is known to be androgen-dependent, the temporal dynamics of postnatal growth remain poorly understood. To delineate the postnatal developmental dynamics of the penis and corpus cavernosum, we established a standardized measurement framework and analyzed their developmental trajectories in mice. Penile and corpus cavernosum growth exhibited a bimodal pattern, with distinct peaks corresponding to the early postnatal period, known as minipuberty, and puberty. The proximal region containing the corpus cavernosum showed more pronounced growth than the distal region mainly composed of os penis, particularly during this early postnatal period. This bimodal growth pattern closely mirrors that of human penile development, highlighting the conserved androgen-responsive developmental programs between mice and humans. Furthermore, early postnatal androgen exposure was sufficient to induce masculinization including increased external genital size and the formation of a corpus cavernosum-like structure in females, whereas later exposure had limited effects. Our findings demonstrate that the early postnatal period, minipuberty, is a critical window for masculinization of external genitalia in mice. These results suggest that the mouse is a valuable model for understanding the developmental mechanisms of the human penis and corpus cavernosum in response to androgens, offering insights into erectile tissue formation and the etiology of congenital penile disorders such as micropenis.