Prostate carcinogenesis induced by N-methyl-N-nitrosourea (mnu) in gerbils: Histopathological diagnosis and potential invasiveness mediated by extracellular matrix components

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Functional and Morphological Reproductive Aspects in Male Rats Exposed to Di-n-Butyl Phthalate (DBP) in Utero and During Lactation

The potential adverse reproductive effects, with emphasis on the epididymis, of in utero and lactational exposure to 100 mg/kg/d di-n-butyl phthalate (DBP) in adult male rat offspring were investigated. The fetal testis histopathology was also determined. The selected endpoints included reproductive organ weights, sperm motility and morphology, sperm epididymal transit time, sperm quantity in the testis and epididymis, hormonal status, fetal testis and epididymal histopathology and stereology, and androgen receptor (AR), aquaporin 9 (AQP9), and Ki-67 immunoreactivities. Pregnant females were divided into two groups: control (C) and treated (T). The treated females received DBP (100 mg/kg/d, by gavage) from gestation day (GD) 12 to postnatal day (PND) 21, while control dams received the vehicle. Some pregnant dams were killed by decapitation on GD20, and testes from male fetuses were collected for histopathogy. Male rats from other dams were killed at PND 90. Fetal testes from treated group showed Leydig-cell clusters, presence of multinucleated germinative cells, and increase of the interstitial component. Testosterone levels and reproductive organ weights were similar between the treated and control adult groups. DBP treatment did not markedly affect relative proportions of epithelial, stromal, or luminal compartments in the epididymis; sperm counts in the testis and epididymis; sperm transit time; or sperm morphology and motility in adult rats. The AR and AQP9 immunoreactivities and proliferation index were similar for the two groups. These results showed that fetal testes were affected by DBP as evidenced by testicular histopathologic alterations, but reproductive parameters and epididymal structure/function were not significantly altered in the adult animals exposed to 100 mg/kg DBP in utero and during lactation.

Effects of altered epididymal sperm transit time on sperm quality

The epididymal sperm transit time seems to have an important role in the process of sperm maturation, and it seems that alterations to the transit can harm the process. The aim of the present work was to evaluate the influence of altered sperm transit time through the epididymis on sperm parameters and fertility of rats, as well as the role of testosterone in the alterations. Sprague-Dawley adult male rats were randomly assigned to four different groups and were treated for 12 days: (i) 10 mu g/rat/day DES, to accelerate the transit; (ii) 6.25 mg/kg/day guanethidine sulphate, to delay the transit; (iii) same treatment as group 1, plus androgen supplementation; (iv) control animals received the vehicles. Guanethidine treatment delayed the sperm transit time through the epididymal cauda, provoking increased sperm reserves in this region. Animals exposed to DES showed an acceleration of sperm transit time in the epididymis, and consequently decreased sperm density in both epididymal regions, the caput-corpus and cauda, and diminished sperm motility. In both cases sperm production was not altered. Testosterone supplementation was able to restore the transit time to values close to normality, as they were higher than in the control rats. The same occurred in relation to sperm motility. Rats exposed to DES presented lower fertility after in utero artificial insemination using sperm collected from the proximal cauda epididymis. Therefore, it was concluded that the acceleration of rat sperm transit time appeared to harm normal sperm maturation, thus decreasing sperm quality and fertility capacity, in an androgen-dependent way.

Orchidopexy restores morphometric-stereologic changes in the caput epididymis and daily sperm production in cryptorchidic mice, although sperm transit time and fertility parameters remain impaired

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oral exposure to methylmercury modifies the prostatic microenvironment in adult rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Combined effect of the finasteride and doxazosin on rat ventral prostate morphology and physiology

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Gestational and Lactational Fenvalerate Exposure on Immune and Reproductive Systems of Male Rats

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparação dos padrões de atratividade de Hermetia illucens (Diptera, Stratiomyidae) associada a carcaças de Rattus norvergicus enterradas e tratadas com hormônios esteróides

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Postnatal growth of the ventral prostate in Wistar rats: A stereological and morphometrical study

Morphological and stereological analyses were used to characterize the growth kinetics of the Wistar rat ventral prostate (VP). Volume density and absolute volume of the epithelium, lumen, smooth muscle cells (SMCs), and nonmuscular stroma were determined by stereology and paired with plasma testosterone levels and different morphometric measurements. The VP shows an initial growth within the first 3 weeks, a resting phase, and the puberal growth. The puberal growth was coincident with the raise in plasma testosterone. Lumen formation occurred within the 3 postnatal weeks. After an expected increase during puberty, the lumen showed a further increase at the 12th week. The volume density of the nonmuscular stroma and of the SMCs decreased slowly postnatally. Absolute volume of the luminal compartment showed three phases of growth (weeks 1-3, 6-9, and 11-12). on the other hand, the increase in the absolute volume of the epithelium was steady up to the 8th week and then showed a marked increase up the 10th week. The increase in epithelial volume was characterized morphologically by the presence of epithelial infoldings and sprouts. The growth of the epithelium showed a 2-week delay as compared to the lumen and occurred only until the 10th week. The epithelial height was variable but could be related to the synthetic activity of the epithelium. In conclusion, the postnatal growth of the VP results from a combination of epithelial proliferation/differentiation and synthesis/accumulation of the secretory products in the lumen.

Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate

Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5alpha-reductase (5alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

Experimental endocrine therapies promote epithelial cytodifferentiation and ciliogenesis in the gerbil female prostate

The incidence of ciliated cells in the prostate gland of the female gerbil (Meriones unguiculatus) is uncommon and apparently becomes more frequent during androgen (testosterone cypionate) and anti-estrogen (letrozole) endocrine therapies. To evaluate the effects of such drug therapies on the induction of ciliogenesis in the glandular epithelium of female prostate glands, adult female gerbils aged 90 days were treated for 14 days with testosterone and letrozole after which their prostate glands were removed for histological, ultrastructural, and serological analyses. The cytodifferentiation of the ciliated phenotype in the alveolar epithelium became more frequent after both the testosterone and the letrozole treatments. The ciliogenesis phenomenon of the epithelial cells in the prostate gland of female gerbils thus appears to be induced by variations in the increase of androgen levels.

Antiestrogen therapies affect tissue homeostasis of the gerbil (Meriones unguiculatus) female prostate and ovaries

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Microscopic evaluation of proliferative disorders in the gerbil female prostate: Evidence of aging and the influence of multiple pregnancies

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Short-term stromal alterations in the rat ventral prostate following alloxan-induced diabetes and the influence of insulin replacement

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)