Comparative Morphology of the Penis and Clitoris in Four Species of Moles (Talpidae).

The penile and clitoral anatomy of four species of Talpid moles (broad-footed, star-nosed, hairy-tailed, and Japanese shrew moles) were investigated to define penile and clitoral anatomy and to examine the relationship of the clitoral anatomy with the presence or absence of ovotestes. The ovotestis contains ovarian tissue and glandular tissue resembling fetal testicular tissue and can produce androgens. The ovotestis is present in star-nosed and hairy-tailed moles, but not in broad-footed and Japanese shrew moles. Using histology, three-dimensional reconstruction, and morphometric analysis, sexual dimorphism was examined with regard to a nine feature masculine trait score that included perineal appendage length (prepuce), anogenital distance, and presence/absence of bone. The presence/absence of ovotestes was discordant in all four mole species for sex differentiation features. For many sex differentiation features, discordance with ovotestes was observed in at least one mole species. The degree of concordance with ovotestes was highest for hairy-tailed moles and lowest for broad-footed moles. In relationship to phylogenetic clade, sex differentiation features also did not correlate with the similarity/divergence of the features and presence/absence of ovotestes. Hairy-tailed and Japanese shrew moles reside in separated clades, but they exhibit a high degree of congruence. Broad-footed and hairy-tailed moles reside within the same clade but had one of the lowest correlations in features and presence/absence of ovotestes. Thus, phylogenetic affinity and the presence/absence of ovotestes are poor predictors for most sex differentiation features within mole external genitalia.

Flutamide-induced hypospadias in rats: A critical assessment.

This paper provides the first detailed description of flutamide-induced hypospadias in the rat based upon wholemount, histologic, three-dimensional reconstruction, scanning electron microscopic, and immunocytochemical analysis. The penile malformations elicited by this potent anti-androgen include a substantial proximal shift in the urethral meatus that clearly conforms to the definition of hypospadias based upon specific morphological criteria for this malformation. Through examination of the normal penile development and flutamide-induced abnormal penile development observed in prenatally oil- and flutamide-treated rats, our analysis provides insights into the morphogenetic mechanism of development of hypospadias. In this regard, a common theme in normal penile development is midline fusion of epithelia followed by removal of the epithelial seam and establishment of midline mesenchymal confluence during development of the penile urethra and prepuce, processes which are impaired as a result of prenatal flutamide treatment. The developmental processes occurring in normal penile development, through comparison with development of female external genitalia and those impaired due to prenatal flutamide treatment, are consistent with critical role of androgen receptors in normal penile development in the rat, and the specific penile abnormalities embodied in flutamide-induced rat hypospadias.

Mouse hypospadias: A critical examination and definition.

Hypospadias is a common malformation whose etiology is based upon perturbation of normal penile development. The mouse has been previously used as a model of hypospadias, despite an unacceptably wide range of definitions for this malformation. The current paper presents objective criteria and a definition of mouse hypospadias. Accordingly, diethylstilbestrol (DES) induced penile malformations were examined at 60 days postnatal (P60) in mice treated with DES over the age range of 12 days embryonic to 20 days postnatal (E12-P20). DES-induced hypospadias involves malformation of the urethral meatus, which is most severe in DES E12-P10, DES P0-P10 and DES P5-P15 groups, and less so or absent in the other treatment groups. A frenulum-like ventral tether between the penis and the prepuce was seen in the most severely affected DES-treated mice. Internal penile morphology was also altered in the DES E12-P10, DES P0-P10 and DES P5-P15 groups (with little effect in the other DES treatment groups). Thus, adverse effects of DES are a function of the period of DES treatment and most severe in the P0-P10 period. In "estrogen mutant mice" (NERKI, ßERKO, αERKO and AROM+) hypospadias was only seen in AROM+ male mice having genetically-engineered elevation is serum estrogen. Significantly, mouse hypospadias was only seen distally at and near the urethral meatus where epithelial fusion events are known to take place and never in the penile midshaft, where urethral formation occurs via an entirely different morphogenetic process.

Diethylstilbestrol-induced mouse hypospadias: "window of susceptibility".

This review presents published and novel results that define the programming window for diethylstilbestrol (DES)-induced abnormal development of the mouse penis. These data indicate that DES has its greatest effect during the period of most intense penile morphogenesis, namely postnatal days 0-15 (P0-P15). Pregnant mice and their neonatal pups were injected subcutaneously with 200 ng/gbw DES every other day from embryonic day 12-18 (DES E12-E18), postnatal day 0-10 (DES P0-P10), embryonic day 12 to postnatal day 10 (DES E12-P10), postnatal day 5-15 (DES P5-P15), and postnatal day 10-20 (DES P10-P20). Aged-matched controls received sesame oil vehicle. After euthanasia at 10, 15, 20 and 60 days, penises were analyzed by gross morphology, histology and morphometry. Penises of all 5 groups of DES-treated mice were reduced in size, which was confirmed by morphometric analysis of internal penile structures. The most profound effects were seen in the DES E12-P10, DES P0-P10, and DES P5-P15 groups, thus defining a DES "programming window". For all parameters, DES treatment from P10 to P20 showed the most mild of effects. Adverse effects of DES on the MUMP cartilage and erectile bodies observed shortly after the last DES injection reverted to normality in the DES P5-P15, but not in the E12-P10 and P0-P10 groups, in which MUMP cartilage and erectile body malformations persisted into adulthood, again emphasizing a "window of susceptibility" in the early neonatal period.

Anatomy of mole external genitalia: Setting the record straight.

Anatomy of male and female external genitalia of adult mice (Mus musculus) and broad-footed moles (Scapanus latimanus) was re-examined to provide more meaningful anatomical terminology. In the past the perineal appendage of male broad-footed moles has been called the penis, while the female perineal appendage has been given several terms (e.g. clitoris, penile clitoris, peniform clitoris and others). Histological examination demonstrates that perineal appendages of male and female broad-footed moles are the prepuce, which in both sexes are covered externally with a hair-bearing epidermis and lacks erectile bodies. The inner preputial epithelium is non-hair-bearing and defines the preputial space in both sexes. The penis of broad-footed moles lies deep within the preputial space, is an "internal organ" in the resting state and contains the penile urethra, os penis, and erectile bodies. The clitoris of broad-footed moles is defined by a U-shaped clitoral epithelial lamina. Residing within clitoral stroma encompassed by the clitoral epithelial lamina is the corpus cavernosum, blood-filled spaces and the urethra. External genitalia of male and female mice are anatomically similar to that of broad-footed moles with the exception that in female mice the clitoris contains a small os clitoridis and lacks defined erectile bodies, while male mice have an os penis and a prominent distal cartilaginous structure within the male urogenital mating protuberance (MUMP). Clitori of female broad-footed moles lack an os clitoridis but contain defined erectile bodies, while male moles have an os penis similar to the mouse but lack the distal cartilaginous structure.