The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development.
The objective of this study was to perform a comprehensive morphologic analysis of developing mouse external genitalia (ExG) and to determine specific sexual differentiation features that are responsive to androgens or estrogens. To eliminate sex steroid signaling postnatally, male and female mice were gonadectomized on the day of birth, and then injected intraperitoneally every other day with DES (200 ng/g), DHT (1 μg/g), or oil. On day-10 postnatal male and female ExG were dissected, fixed, embedded, serially sectioned and analyzed. We identified 10 sexually dimorphic anatomical features indicative of normal penile and clitoral differentiation in intact mice. Several (but not all) penile features were impaired or abolished as a result of neonatal castration. Those penile features remaining after neonatal castration were completely abolished with attendant clitoral development in androgen receptor (AR) mutant male mice (XTfm/Y and X/Y AR-null) in which AR signaling is absent both pre- and postnatally. Administration of DHT to neonatally castrated males restored development of all 10 masculine features to almost normal levels. Neonatal ovariectomy of female mice had little effect on clitoral development, whereas treatment of ovariectomized female mice with DHT induced partial masculinization of the clitoris. Administration of DES to neonatally gonadectomized male and female mice elicited a spectrum of development abnormalities. These studies demonstrate that the presence or absence of androgen prenatally specifies penile versus clitoral identity. Differentiated penile features emerge postnatally and are sensitive to and dependent upon prenatal or pre- and postnatal androgen. Emergence of differentiated clitoral features occurs postnatally in either intact or ovariectomized females. It is likely that each penile and clitoral feature has a unique time-course of hormonal dependency/sensitivity.
Purpose Results following distal hypospadias repair are favorable. Grouping proximal and distal hypospadias repair artificially increases the perceived success rate of proximal hypospadias. We identified our complication rate of proximal hypospadias repair and hypothesized a higher complication rate for 1-stage repair. Materials and Methods We retrospectively reviewed the records of consecutive boys who underwent proximal hypospadias from 2007 to 2014. Proximal hypospadias was defined as a urethral meatus location at or more proximal than the penoscrotal junction after penile degloving. We further stratified boys into those with planned 1-stage vs 2-stage repair. Univariate and Cox regression analyses were performed to assess associations with covariates and compare time to the first complication, respectively. Results A total of 167 boys met study inclusion criteria. Median followup was 31.7 months for 1-stage repair in 86 patients and staged repair in 81. The overall complication rate was 56%. Complications developed in 53 of 86 1-stage (62%) vs 40 of 81 staged (49%) repairs (p = 0.11). The number of unplanned procedures per patient was higher in the 1-stage than in the staged group (0.99 vs 0.69, p = 0.06), as was the number of patients who had at least 2 complications (29 of 86 or 33% vs 13 of 81 or 16%, p = 0.03). Cox regression showed no difference in time to the first complication for staged compared to 1-stage repair (HR 0.77, 95% CI 0.43–1.39). Conclusions Our 56% complication rate of proximal hypospadias warrants further long-term patient followup. More patients in the 1-stage group experienced at least 2 complications. However, when complications developed, they developed no differently in the 2 groups.
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