Stromal Development in the Ventral Prostate, Anterior Prostate and Seminal Vesicle of the Rat

Abstract

The prostate and seminal vesicle (SV) are androgen-dependent secretory glands of the male genital tract. They produce the bulk of the seminal secretions. The object of the present study was to examine and document the ontogeny of stromal maturation in the rat anterior and ventral prostate and SV. These organs have a loosely organized cellular mesenchyme during fetal development. During prostatic development the mesenchyme condensed to form smooth muscle sheaths immediately surrounding the epithelium, with looser connective tissue between individual ducts. In the SV, a loose connective tissue layer called the lamina propria lies between the epithelium and developing muscle. Smooth muscle oc-actin, myosin, desmin, laminin, vinculin, vimentin and androgen receptor (AR) expression were examined by immunocytochemical methods during the pre- and postnatal developmental periods. The first marker to be detected was vimentin, which was initially found throughout the mesenchyme. During development vimentin became mostly restricted to the interductal tissue of the prostate and the lamina propria of the SV. Smooth muscle markers were expressed in an orderly sequence in a proximal to distal manner along prostatic ducts, from the urethra towards the tips. Expression of oc-actin was followed by vinculin, myosin, desmin, and laminin. These markers became localized to the developing smooth muscle sheaths and were not expressed in the interductal tissue of the prostate or the lamina propria of the SV. Organ culture experiments demonstrated that androgens were required for the differentiation of smooth muscle sheaths. Castration of adult rats demonstrated that androgens were required to maintain smooth muscle differentiation. In castrates, the stroma was relatively thicker but less dense than in intact animals. Following castration, expression of the smooth muscle markers was lost sequentially in the reverse order of their expression during development. In long-term castrates oc-actin, vimentin and a small amount of vinculin were detected. AR were first detected in the urogenital sinus mesenchyme immediately surrounding the epithelium at 16 days of gestation. As development progressed expression of AR became more widespread, and postnatally was found throughout the mesenchyme. As maturation of smooth muscle occurred, stromal expression of AR became localized to the muscular sheath immediately surrounding the epithelium. In the prostate the interductal connective tissue displayed very low levels of AR expression. In the SV, AR were also observed in the lamina propria. In summary, stromal differentiation and dedif-ferentiation in the rat prostate and SV were found to be androgen-dependent processes with ordered sequential ontogenic expression of specific markers.

Dynamics of the Epithelium During Canalization of the Rat Ventral Prostate

“…It is important to realize that the major structural modification during the first postnatal week is canalization, as stereology showed no significant changes in the volumes of epithelium and stroma, which appears to take place later on (Donjacour and Cunha, 1988;Hayward et al, 1996b;Vilamaior et al, 2006).…”

Prostate-specific Klf6 Inactivation Impairs Anterior Prostate Branching Morphogenesis through Increased Activation of the Shh Pathway

“…During development, the mesenchyme condenses around the ducts in a proximal to distal fashion to encase the ducts with smooth muscle actin (SMA), the earliest smooth muscle marker expressed, and desmin, a later marker (33). To determine the state of smooth muscle differentiation, we examined the expression of SMA and desmin at P5, which corresponds to the initiation of secondary branching in the anterior prostate.…”

“…On the other hand, it is also possible that the continuous layer of smooth muscle formed around the main ducts as a result of the absence of branching. To further understand this branching defect, we examined expression of androgen receptor by immunofluorescent staining, because several investigators had demonstrated that postnatal prostate branching morphogenesis and differentiation of the stroma are highly regulated by androgen (32,33,35). Androgen receptor was expressed continuously around the primary and secondary ducts of Klf6 f/f Nkx3.1 ϩ/ϩ (supplemental Fig.…”

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

“…3). For example, cells of the embryonic UGM form a layer of smooth muscle, which lines the epithelium and exhibits contractile activity to aid expulsion of prostatic fluid into the ejaculate (Hayward et al, 1996b). The adult prostate stroma also contains a large population of mature fibroblasts that secrete extracellular matrix, consisting of fibrillar proteins, glycoproteins and proteoglycans that form a structural network and mediate growth factor signaling (Tuxhorn et al, 2001).…”