Neonatal exposure to aluminum chloride predisposes adult and senile gerbils to the prostatic hyperplasia.

Several pollutants can alter neonatal prostatic development predisposing this gland to diseases. The toxicity and endocrine disrupting potential of aluminum has been reported in many organs, but little is known about its effects on the prostate. This study aimed to evaluate the effects that aluminum neonatal exposure can cause in the male ventral prostate and in the female prostate of adult and senile gerbils. Male and female pups were treated orally with aluminum chloride (10 mg/kg) from the 1st to the 14th day life. After treatment, the animals were aged until they reached 90 days or 1 year of life. The prostate glands were dissected out and submitted to morphological, immunohistochemical and ultrastructural analyses. Ventral prostates of adult males showed moderate hyperplasia and increased epithelial proliferation not associated with androgen receptor (AR) deregulation. On the other hand, senile males showed intense prostatic hyperplasia, and increased cell proliferation and epithelial AR regulation. Additionally, at both ages, there was a reduction in the prostate secretory function. The morphological changes observed in the female prostate were like those found in males. However, in adult females, prostatic hyperplasia was accompanied by a lower regulation of AR and estrogen receptor alpha, while in senile females, intense hyperplastic growth was associated with an increase in estrogen receptor alpha and a reduction in stromal AR. These results demonstrate that aluminum chloride neonatal exposure alters the hormonal regulation of the male and female prostate, inducing tissue damage that occurs in adulthood and intensifies during aging.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

Aluminum intake in the neonatal phase disrupts endochondral ossification in rodents.

OBJECTIVE: This study evaluated the effects of aluminum (Al) intake on endochondral ossification during the neonatal phase. METHOD: Twelve male newborn Gerbils (Meriones unguiculatus) were randomly divided into control (C) and aluminum (Al) groups (n = 6 animals/group). From the 1st to 15th day of life, gerbils received an AlCl3 solution (10 mg/kg/day) via gavage. The control group received only the saline solution. On the 16th day, their tibias were processed for paraffin embedding and were submitted to histomorphometric, histochemical, and immunohistochemical analyses. RESULTS: In the epiphyseal cartilage Al did not affect the proteoglycan content or cell proliferation; however, it increased matrix metalloprotease-2 (MMP-2) immunostaining and the hypertrophic layer thickness. In bone, Al decreased trabeculae number, trabecular width, cortical bone width, and proliferation. Furthermore, the relative frequency of bone matrix and fibrillar collagen decreased 3.9% and 16.2%, respectively. The number of osteoclasts and osteocalcin digital optical density (D.O.D) remained the same. CONCLUSION: The results suggest that Al intake during the neonatal period impairs endochondral ossification by affecting epiphyseal cartilage and bone architecture.

Subacute exposure to aluminum chloride causes prolonged morphological insults in the ventral male prostate and in the female prostate of adult gerbils.

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10 mg/kg) for 30 consecutive days. The animals were euthanized 1 day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.

The Influence of Pregnancy on Female Prostate Morphophysiology in Gerbils (Meriones unguiculatus).

Morphophysiological changes of the female prostate during pregnancy are still little known. Considering that this gland is highly influenced by steroid hormones, the aim of this study was to evaluate the impact of the pregnancy on female prostate morphophysiology in gerbils. Pregnant females were timed, and the prostates were analyzed at pregnancy days 6 (P6), 12 (P12), 18 (P18), and 24 (P24). Virgin females were used as the control group (C). We observed a profound change in the hormonal profile during gestation, which was marked by a high oscillation of the progesterone (P4) hormone. P4 serum levels increased, peaking at the middle of gestation, and decreased to the end of the pregnancy. The morphology of the gland in pregnant females also changed, being marked by an increase of acini lumen, and a decrease in stroma. Indeed, the acinar changes during pregnancy were followed by a significant reduction of the epithelial height, besides a change of the smooth muscle cells' morphology that became more relaxed. The number of progesterone receptor (PR) and androgen receptor (AR)-positives cells decreased with the increase of progesterone serum levels, showing an inverse relationship. Finally, we observed a reduction of epithelial proliferation and a significant increase of gland PAS-positive secretion at the end of pregnancy. Altogether, these results showed, for the first time, that the female prostate morphophysioloy is profoundly influenced by the gestational period, suggesting that the fluctuation of the P4 serum levels is the main factor influencing the gland during this period.

Neonatal exposure to aluminum chloride disrupts branching morphogenesis and hormonal signaling of the ventral male prostate and female prostate of gerbils.

BACKGROUNG: Exposure to environmental pollutants in critical developmental windows may predispose the prostate to permanent changes in its homeostasis. Thus, it is essential to know the effects that environmental toxics, such as aluminum, can cause during the development of this gland. The aim of this study was to evaluate the effects of neonatal aluminum exposure on the ventral male prostate and the female prostate of 15 days old gerbils. METHODS: Male and female gerbils were exposed orally to 10 mg/kg/day of aluminum chloride from the 1st to the 14th postnatal day life. At 15 days of life, gerbils were euthanized and their prostates were collected for biometric, morphological, morphometric, immunohistochemical and three-dimensional reconstruction analyzes. RESULTS: Al exposure caused a reduction in body weight in males and a significant increase in serum testosterone levels in females. Prostate branching morphogenesis was intensified in males, who had greater length, number and area of prostatic epithelial buds. Additionally, Al altered the prostate hormonal regulation of males and females, causing up regulation of the androgen receptor and estrogen receptor alpha in the female prostate, and increased immunostaining of the androgen receptor in the ventral male prostate. These changes were associated with an increased rate of epithelial and stromal cell proliferation in both sexes. CONCLUSION: Together, these results indicate that Al altered the neonatal development of the prostate and that this metal acted as an endocrine disruptor in this gland.

Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils.

Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.

Developmental changes induced by exogenous testosterone during early phases of prostate organogenesis.

The aim of this study was to evaluate the impact of prenatal testosterone exposure on prostate development in male and female neonatal gerbils. Pregnant females were exposed to subcutaneous injections of testosterone cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were then euthanized at postnatal day 1. Morphological analysis showed that females were severely affected by androgen exposure. We also observed that male and female urogenital sinus (UGS) responded differentially to testosterone treatment, demonstrating heterogeneous immunostaining for the androgen receptor (AR), estrogen receptor alpha (ERα), and proliferating cell nuclear antigen (PCNA). Smooth muscle α-actin (α-SMA) analysis showed that testosterone delays the myodifferentiation, allowing buds to reach the ectopic mesenchymes of the female UGS. Our data showed that abnormal testosterone exposure disrupted prostate organogenesis, altered the expression patterns of important markers, and demonstrated that female UGS was particularly influenced by androgen exposure during a critical window in the developmental period.

Photobiomodulation and Mandibular Advancement Modulates Cartilage Thickness and Matrix Deposition in the Mandibular Condyle.

Objective: We evaluated the effects of photobiomodulation (PBM), mandibular advancement (MA), and the combination of both treatments (PBM+MA) on condylar growth, by the analysis of cartilage and bone formation, fibrillar collagen deposition, proteoglycan content, cell proliferation, and clastic cell index (CCI). Methods: Forty male Wistar rats were randomly assigned to CONTROL, PBM, positive control-MA, and PBM+MA groups. The appliance was worn 10 h/day. Laser was irradiated bilaterally on mandibular condyles in 8 alternate days (1 irradiation point per condyle) using the following parameters: 780 nm, 10 J/cm2, 40 mW, 1 W/cm2, 10 sec/point, 0.4 J/point, and cumulative dose per point: 3.2 J. PBM+MA received both treatments simultaneously. After 15 days, the animals were euthanized and the condyles dissected and embedded in paraffin. Histological sections from the intermediate portion of the condyle were used for morphometric analysis. The relative frequency (%) of fibrillar collagens was determined in sections stained with picrosirius red-hematoxylin under polarized light or Gömöri's method for reticular fibers. Proteoglycan content was evaluated by computerized photocolorimetric analysis. CCI was determined by tartrate-resistant acid phosphatase (TRAP), and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Results: PBM and MA influenced condylar cartilage thickeness and matrix deposition, but none of the treatments affected significantly the area of the condyle. CCI were not influenced by the treatments, but clastic cells distribution was influenced by MA and PBM+MA treatments. There was no significant difference in proliferating cells among the groups. Conclusions: This study demonstrated that PBM and MA stimulates matrix deposition and cartilage thickening in the mandibular condyle, but was not able to demonstrate a synergistic effect between the treatments. Additional studies should be conducted to evaluate the possible synergistic effect between PBM and MA.

Bisphenol-S promotes endocrine-disrupting effects similar to those promoted by bisphenol-A in the prostate of adult gerbils.

This study evaluated the effects of BPS (40 µg/kg/day, during 28 consecutive days) on the male ventral prostate and female prostate of adult gerbils. For comparative purposes, gerbils were also exposed to BPA under the same experimental conditions. The prostates were submitted to biometric, morphometric, histopathological, immunohistochemical and ultrastructural analyses. The results demonstrated that exposure to both types of bisphenol caused no changes in testosterone or estradiol serum levels. Morphologically, the effects of BPS and BPA on female prostates were similar and included changes in prostatic tissue compartments, glandular hyperplasia, AR and ERα up-regulation and increased cell proliferation. In males, BPS and BPA promoted differential effects, since the prostate presented morphological changes and proliferative disorders that were more pronounced in the BPS group. Therefore, this study demonstrates that BPS caused endocrine disruption in the prostate of male and female gerbils.

Bisphenol-A promotes antiproliferative effects during neonatal prostate development in male and female gerbils.

The aim of this study was to evaluate the development of male and female neonatal gerbil prostate under normal conditions and exposed to bisphenol-A (BPA). Normal postnatal development of the female gerbil prostate occurs earlier than and is morphologically distinct from that occurring in males. In BPA-exposed PND8 gerbils, we have not observed evidence of alterations in the ductal branching in either gender. However, the exposure to BPA alters the immunolabeling pattern of AR, ERα, and PCNA. In males, the exposure to high dosages of BPA resulted in a decrease in the proliferative status of the developing ventral prostate. In females, both high and low dosages were sufficient to decrease the proliferation of paraurethral buds in the branching process by more than 50%. Therefore, the obtained data indicate that BPA promotes antiproliferative effects during the neonatal development of the gerbil prostate, with more sensitivity to this endocrine disruptor in females.

Budding process during the organogenesis of the ventral prostatic lobe in Mongolian gerbil.

The prostate is a mammalian gland that shows a complex process of organogenesis. Here, a morphological study to characterize the organogenesis of the ventral prostate lobe in male gerbils was conducted. The urogenital sinus (UGS) was dissected out and processed for paraffin embedding. Histological sections were subjected to cytochemical, immunofluorescence, immunohistochemical, and three-dimensional reconstruction techniques. We found that the first ventral buds emerged from the ventral urethral epithelium between the days 20 and 21 of prenatal life, reaching the ventral mesenchymal pad and initiating the branching process on the first day of postnatal life. The buds presented a V-shaped elongation, suggesting that the smooth muscle layer (SML) plays an important role during budding events. Indeed, whereas the androgen receptor (AR) was preferentially found in the UGS mesenchyme (UGM), estrogen receptor alpha (ERα) was localized in both the UGM and in the emerging buds. This study characterized the morphological aspects of the budding process in a different rodent from rat and mice, serving as a new model for future studies on developmental biology of the prostate.

Exposure to ethinylestradiol during prenatal development and postnatal supplementation with testosterone causes morphophysiological alterations in the prostate of male and female adult gerbils.

Steroids perform significant functions in prostatic development and growth, so that interferences of this equilibrium may predispose the gland to the development of diseases during the life. Embryonic and neonatal exposure to xenoestrogens, many of them with endocrine-disrupting potential, has been related to the induction of disturbances in reproductive system organs. Thus, this study aimed to analyse morphological and immunocytochemical aspects of prostate in both male and female adult gerbils either exposed to ethinylestradiol during the prenatal phase (pregnant females received 10 µg/kg, by gavage) (EE group) or exposed to testosterone (1 mg/kg) during the postnatal period (EE/T group). Serological analysis revealed a rise in estradiol levels in adult males and females of the EE group. A higher incidence of prostatic intraepithelial neoplasia (PIN) was observed in the male and female prostate of the treated groups, besides an increase in collagen and reticular fibres. Immunocytochemistry showed an increase in prostatic epithelial cells immunoreactive to AR and a presence of a smooth muscle layer, evidenced by α actin, in injured regions this way absent in prostatic epithelial buds. These pieces of evidence suggest that the alterations verified in the prostate in adulthood of both sexes may be due to the high oestrogen levels. Either males or females of the EE/T group showed normalized estradiol levels, although prostatic lesions could be observed. While the prostatic gland of male gerbils was more affected than the female prostate, this study showed that the exposure to EE during this critical period of development disrupts the prostate of both sexes in terms of prostatic lesions.