Correctional Change Through Neuroscience

Currently, the U.S. criminal justice system is under intense scrutiny. High- profile cases question the appropriateness of specific types of evidence, decision making in sentencing, and the treatment of convicted offenders. Clearly, these issues are not new. And, as has been historically the case, the justice system looks toward science for assistance in addressing and redressing problems with the delivery of justice

Development of the human prepuce and its innervation.

Development of the human prepuce was studied over the course of 9-17 weeks of gestation in 30 specimens. Scanning electron microscopy revealed subtle surface features that were associated with preputial development, namely the appearance of epidermal aggregates that appeared to be associated with formation of the preputial fold. Transverse and sagittal sections revealed that the epidermis of the glans is considerably thicker than that of the penile shaft. We described a novel morphogenetic mechanism of formation of the preputial lamina, namely the splitting of the thick epidermis of the glans into the preputial lamina and the epidermis via the intrusion of mesenchyme containing red blood cells and CD31-positive blood vessels. This process begins at 10-11 weeks of gestation in the proximal aspect of the glans and extends distally. The process is likely to be androgen-dependent and mediated via androgen receptors strategically localized to the morphogenetic process, but signaling through estrogen receptor may play a role. Estrogen receptor alpha (ESR1) has a very limited expression in the developing human glans and prepuce, while estrogen receptor beta (ESR2) is expressed more broadly in the developing preputial lamina, epidermis and urethra. Examination of the ontogeny of innervation of the glans penis and prepuce reveals the presence of the dorsal nerve of the penis as early as 9 weeks of gestation. Nerve fibers enter the glans penis proximally and extend distally over several weeks to eventually reach the distal aspect of the glans and prepuce by 14-16 weeks of gestation

Clitoral development in the mouse and human.

The goal of this report is (a) to provide the first detailed description of mouse clitoral development, and (b) to compare mouse and human clitoral development. For this purpose, external genitalia of female mice were examined by wholemount microscopy, histology and immunohistochemistry from 14 days of gestation to 10 days postnatal. Human clitoral development was examined by these techniques as well as by scanning electron microscopy and optical projection tomography from 8 to 19 weeks of gestation. The adult mouse clitoris is an internal organ defined by a U-shaped clitoral lamina whose development is associated with the prenatal medial and distal growth of the female preputial swellings along the sides of the genital tubercle to form the circumferential preputial lamina. Regression of the ventral aspect of the preputial lamina leads to formation of the U-shaped clitoral lamina recognized as early as 17 days of gestation. While the adult U-shaped mouse clitoral lamina is closely associated with the vagina, and it appears to be completely non-responsive to estrogen as opposed to the highly estrogen-responsive vaginal epithelium. The prominent perineal appendage in adult females is prepuce, formed via fusion of the embryonic preputial swellings and is not the clitoris. The human clitoris is in many respects a smaller anatomic version of the human penis having all of the external and internal elements except the urethra. The human clitoris (like the human penis) is derived from the genital tubercle with the clitoral glans projecting into the vaginal vestibule. Adult morphology and developmental processes are virtually non-comparable in the mouse and human clitoris

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

Contrasting mechanisms of penile urethral formation in mouse and human.

This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed