Sexual differentiation in the male and female mouse from days 0 to 21: A detailed and novel morphometric description

Purpose We hypothesized that a significant portion of sexual differentiation of mouse external genitalia occurs postnatally. To establish a baseline of normal development to which genital abnormalities could be compared, we determined morphometric measurements and morphological descriptions of the postnatal period of sexual differentiation in mice from birth to 21 days postnatally. Materials and Methods The external genitalia of male and female CD-1® mice were serially sectioned for histological staining. Mice were studied by age group, including ages 0 to 1, 2 to 3, 4 to 5, 10 and 21 days. Three-dimensional reconstructions were created to visually compare differences. Morphometric measurements were made of the distal mouse external genitalia and compared across age groups, and between males and females. Results The morphology of male and female mouse external genitalia is similar at 0 to 1 days but undergoes dramatic changes during 21 days. The changes include the development of mesenchymal extensions, which in males form the male urogenital mating protuberance and erectile bodies, as well as comparable structures in females. Differences in morphometric measurements in homologous males and females became pronounced during 0 to 21 days, serving as a baseline for recognizing the genesis of malformations of the mouse external genitalia. Conclusions Male and female mouse external genitalia are similar morphologically and morphometrically at birth but achieve dramatic differences by age 21 days, suggesting that a significant portion of sexual differentiation in the mouse occurs after birth. We described these changes using novel, accurate morphometric measurements and 3-dimensional reconstruction. These results will be useful for studying abnormal sexual development of the mouse external genitalia.