Sodium overload during postnatal phases impairs diastolic function and exacerbates reperfusion arrhythmias in adult rats.

Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p < 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p < 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.

A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Impacts of heavy metal exposure on the prostate of murine models: Mechanisms of toxicity.

Heavy metals are elements found into the environment mainly due to anthropogenic activities. Naturally occurring and higher released doses cause disorders in the prostate, which depends on appropriate hormonal regulation, and exposure to heavy metals may impair prostate homeostasis. The current work highlighted the main mechanisms of toxicity of different environmental heavy metal contaminants, such as aluminum, arsenic, cadmium, chromium, lead, mercury, and nickel, and their impacts found in the prostate morphophysiology of murine models. The repercussions triggered by heavy metals on the prostate include hormonal imbalance and oxidative damage, leading to morphological alterations, which can vary according to the chemical properties of each element, exposure time and concentration, and age. The information of altered biological pathways and its impacts on the prostate of exposed murines are related to human outcomes being useful in the real context of human exposure.

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.

Protective effects of chrysin against the neurotoxicity induced by aluminium: In vitro and in vivo studies.

Chronic exposure to aluminium (Al) can contribute to the progression of several neurological and neurodegenerative diseases. Al is a metal that promotes oxidative damage leading to neuronal death in different brain regions with behavior, cognition, and memory deficits. Chrysin is a flavonoid found mainly in honey, passion fruit, and propolis with antioxidant, anti-inflammatory, and cytoprotective properties. In this study, we used an integrated approach of in vitro and in vivo studies to evaluate the antioxidant and neuroprotective effects of chrysin against the neurotoxicity elicited by aluminium chloride (AlCl3). In in vitro studies, chrysin (5 µM) showed the ability to counteract the early oxidative stress elicited by tert-butyl hydroperoxide, an oxidant that mimics the lipid peroxidation and Fenton reaction in presence of AlCl3 as well as the late necrotic death triggered by AlCl3 in neuronal SH-SY5Y cells. In vivo studies in a mouse model of neurotoxicity induced by chronic exposure to AlCl3 (100 mg/kg/day) for ninety days then corroborated the antioxidant and neuroprotective effect of chrysin (10, 30, and 100 mg/kg/day) using the oral route. In particular, chrysin reduced the cognitive impairment induced by AlCl3 as well as normalized the acetylcholinesterase and butyrylcholinesterase activities in the hippocampus. In parallel, chrysin counteracted the oxidative damage, in terms of lipid peroxidation, protein carbonylation, catalase, and superoxide dismutase impairment, in the brain cortex and hippocampus. Lastly, necrotic cells frequency in the same brain regions was also decreased by chrysin. These results highlight the ability of chrysin to prevent the neurotoxic effects associated with chronic exposure to Al and suggest its potential use as a food supplement for brain health.

Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.

The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.

Therapeutic effects of ß-caryophyllene on proliferative disorders and inflammation of the gerbil prostate.

BACKGROUND: The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. ß-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone. METHODS: Animals were distributed into four groups (n = 8/group): Intact control (C); ß-Caryophyllene (BCP): ß-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and ß-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed. RESULTS: Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells. CONCLUSION: BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH.

Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration.

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate.

The aim of this study was to evaluate whether high levels of exogenous testosterone (T) interfere in prostate morphogenesis. Pregnant females were exposed to subcutaneous injections of T cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were euthanized at postnatal days 1 and 15. 15-day-old males had only fibroblast growth factor 10 (FGF10) immunostaining and nuclear form factor altered by the treatment, whereas treated females (T1 and T15) had almost all analyzed parameters changed. T1 females showed an increased anogenital distance (AGD), whereas T15 females had both AGD and ovary weight increased. T1 females had a higher number of epithelial buds emerging from the urethral and vaginal epithelium. We observed ectopic prostatic tissue surrounding the vagina in both T1 and T15 females. Moreover, the ectopic acini of T15 females showed delayed luminal formation, and there was a thickening of the periacinar smooth muscle layer (SML). Finally, FGF10 immunostaining intensity decreased in both T15 male and female prostates. Indeed, Sonic hedgehog (Shh) was upregulated in T15 female prostates, whereas no difference was observed between the male groups. These data showed that exogenous T changed the nuclear morphology of prostate epithelial cells in both males and females. Surprisingly, smooth muscle hyperplasia was also observed in the ectopic female prostate. Moreover, T downregulated FGF10 in both male and female prostates. Interestingly, the results suggest that FGF10 downregulation is mediated by the upregulation of Shh in females. In conclusion, exogenous T disrupts prostate development, particularly, affecting, the female.

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.

The number and periodicity of seizures induce cardiac remodeling and changes in micro-RNA expression in rats submitted to electric amygdala kindling model of epilepsy.

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration.

Design, synthesis and pharmacological assessment of new pyrazole compounds.

AIMS: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. MAIN METHODS: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall-Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. KEY FINDINGS: The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.

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.

"Prostate telocytes change their phenotype in response to castration or testosterone replacement".

Telocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte's phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells "telocytes with a synthetic phenotype". As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.