Disorders related with ageing in the gerbil female prostate (Skene's paraurethral glands)

Abstract

The female organs, which are regulated by steroid hormones, are targets of studies especially those related to senescence. However, although the female prostate is an organ influenced by hormones and susceptible to lesions, there is still little information about its histopathology. Thus, given the morphophysiological similarity between the prostate in women and female gerbils, the present study aimed to identify the spontaneous histopathological changes in this rodent to provide contributions to the understanding of lesions that also affect the human female prostate. The structural, ultrastructural, immunohistochemical, morphometric-stereological and serological aspects, as well as the quantification of the incidence, multiplicity and percentage of acini affected by different lesions were analyzed. Benign prostate lesions including hyperplasia, prostatitis, microcalculi and calculi; preneoplastic lesions like dysplasias; premalignant lesions, such as high grade prostatic intraepithelial neoplasia as well as malignant ones, specifically adenocarcinoma, were identified in the adult gland, but they were intensified during senescence, which is possibly due to the imbalance among steroid hormone levels. Although clinical attention focuses on other urogenital organs, the real condition of the histopathological injuries in the human female prostate should be considered. A serious preventive work regarding the female prostate could be applied in the gynaecological context in order to monitor the gland and avoid possible disturbances to women's health and consequently provide better quality of life.

Figure 1

(a) Structural aspects of the control young female prostate. General view of the gland (g) with epithelium compartment (ep) inserted in the fibromuscular stroma (s) H&E. Bar 200 μm. (b–h) Histopathological aspects of the female prostate disorders in old gerbil stained by H&E. (b) Gland general aspect with epithelial hyperplasia. Stratified secretory epithelium (ep) inserted in dense stroma (s). Bar 100 μm. (c) General view of an acinus with intraepithelial neoplasia (PIN) containing several intraepithelial arcs (*). Bars 200 μm. (d) Alveolus with dysplasia and prostatic calculi (arrows) scattered although lumen (l) (smc smooth muscular cells, bv blood vessel). Bars 200 μm. (e) General view of an acinus with intraepithelial neoplasia (PIN) containing several intraepithelial arcs (*). To this lesion is associated inflammatory cells (ic). Bars 100 μm. (f) Detail of the gland showing the atrophic epithelium with extremely flat cells and microcalculi disperse throughout the lumen (l) (co collagen). Bar 50 μm. (g–h) Epithelial compartment (ep) proliferated showing prostatic intraepithelial neoplasia (PIN) and atypical cells. Bar 10 μm.

Figure 2

Histopathological aspects of the female prostate in old gerbil. (a) Gland alveolus showing morphologic disarrangement and cellular proliferation (left) distinguishing the adenocarcinoma contrasting with normal alveolus (right) (ep epithelium, l lumen, s stroma, smc smooth muscular cells, bv blood vessel). H&E. Bar 100 μm. (a’) Detail of anomalous cell proliferation with inflammatory cells (arrows). Bar 20 μm. (b) Disarrangement of the reticular fibre (left) distinguishing the adenocarcinoma contrasting with normal one (right) (ep epithelium, l lumen, s stroma, bv blood vessel). Gömöri's stain. Bar 100 μm. (b’) Detail of the fragmentation reticular fibres network in the basal lamina (double arrows) and stroma (arrows). Bar 20 μm. (c) In the normal acini, continuous basal lamina (double arrows) and organized reticular fibres network (arrows) is observed (l lumen, ep epithelium). Gömöri's stain. Bar 20 μm. (d) Anomalous epithelium cells proliferated with local invasion to stroma (arrowheads) associated with inflammatory cells distinguishing the adenocarcinoma of the gland (asterisk prostatitis, ep epithelium, bv blood vessel). H&E. Bar100 μm. (e) Adenocarcinoma of the gland stained by Feulgen reaction. (arrowheads epithelium cells proliferated, asterisk prostatitis). Bar 100 μm. (f) Detail of the base's epithelium, stained by Gömöri's stain, where can observe disrupted subepithelial (double arrows) reticular fibres and in the stroma (arrows) (asterisk epithelium cells). Bar 20 μm. (g) Detail of adenocarcinoma stained by Feulgen reaction showing different intensity of reaction in the chromatin. Note that dark inflammatory cells (arrows) and clear epithelial tumour cells (asterisk) (ep epithelium, s stroma). Bar 20 μm.

Figure 3

PCNA immunocytochemistry counterstained by haematoxylin. (a–c) Epithelial compartment of control female prostate free of the histopathology disorders. Demarcation of nuclear proliferation is very low in normal epithelium (immunoreactive nucleus is brown). Bars: (a) 200 μm, (b) 100μm, (c) 50 μm. (d–h) Hyperplasic secretory epithelial compartment with large number of positive PCNA cells. Bars: (d,e) 200 μm, (f–h) 50 μm.

Figure 4

Ultrastructural aspects of the senile female prostate exhibiting disorders histopathology. (a) Squamous epithelium constitutive by secretory cells (sc) of heterogeneous phenotype and voluminous nucleus (n), with lipid droplets (white arrows) dispersed although cytoplasm and microvillous (black arrows) in its apical superficies. Dense stroma containing abundant collagen fibres (co) and smooth muscular cells (smc) which are below of the continuous basement membrane (bm). Bar 5.5 μm. Inset: Detail of the basal lamina showing the ultrastructural integrity. Bar 1.0 μm. (b) Detail of the intraepithelial arcs in early stage (n nucleus). Bar 1.86 μm. (d) Microlumens (full arrows) characteristics of the PIN high grade with cribriform pattern (sc secretory cell, n nucleus, dark arrows microvilous). Bar 0.7 μm. (e) Shown are fenestrations (full arrows) in the basement membrane (bm) allowing the contact between epithelial and stromal compartments designating a possible malignant disorder (n nucleus, co collagen). Bar 0.7 μm.