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1.
Microsc Microanal ; 29(2): 635-648, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37749728

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by elevated arterial pressure and vascular resistance. PAH may cause alterations in the microcirculation of several organs, including the kidney, liver, brain, and testes. However, it remains unclear whether monocrotaline-induced PAH exerts detrimental effects on animal testes. Thus, we analyzed the impact of PAH on testicular morphology and function. Additionally, we investigated the effect of resistance exercise training (RT) on testicular parameters in PAH rats. Eight healthy Wistar rats and eight PAH rats were subjected to RT training for 30 days; the other PAH and healthy rats (n = 8/group) did not exercise. PAH rats had lower reproductive organ weight, serum testosterone levels, testicular glucose, and nitric oxide (NO) levels, Leydig cell parameters, tubular morphometry, germ cell counts, and daily sperm production than healthy animals did. The practice of RT attenuated the negative impact of PAH on the relative weights of the testes and epididymides, Leydig cell number, nuclear volume, testicular NO levels, and seminiferous epithelium architecture. Moreover, RT positively influenced testosterone levels in PAH animals. We conclude that PAH exerts deleterious effects on testicular histology and function. However, RT can be beneficial to the PAH-affected testicular parameters.


Assuntos
Hipertensão Arterial Pulmonar , Treinamento Resistido , Masculino , Ratos , Animais , Humanos , Ratos Wistar , Testículo , Sêmen , Testosterona
2.
Environ Toxicol ; 38(5): 1162-1173, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36757007

RESUMO

Arsenic is an environmental toxicant known to be a carcinogen and endocrine disruptor. Maternal exposure to arsenic has been associated with fetus malformation and reproductive disorders in male offspring. However, it is unclear the extent to which those effects remain during postnatal development and adulthood. Therefore, this study aimed to investigate the long-term effects of prenatal arsenic exposure on reproductive parameters of male offspring at peripubertal and adult periods. Pregnant female Wistar rats were exposed to 0 or 10 mg/L sodium arsenite in drinking water from gestational day 1 (GD 1) until GD 21 and male pups were analyzed at postnatal day 44 (PND 44) and PND 70. We observed that some reproductive parameters were affected differently by arsenic exposure at each age evaluated. The body and reproductive organs weights, as well as testicular and epididymal morphology were strongly affected in peripubertal animals and recovered at adult period. On the other hand, the antioxidant genes expression (SOD1, SOD2, CAT and GSTK1) and the endogenous antioxidant system were affected in the testes and epididymides from both peripubertal and adult rats. Finally, an impairment in daily sperm production and in sperm parameters was observed in adult animals. Taken together, our findings show that prenatal arsenic exposure affected reproductive parameters of peripubertal and adult male rats mainly due to oxidative stress. Collectively, those alterations may be affecting fertility potential of adult animals.


Assuntos
Arsênio , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Ratos , Masculino , Animais , Feminino , Ratos Wistar , Sêmen , Reprodução , Testículo
3.
Pharmacol Res ; 177: 106117, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124205

RESUMO

Visceral leishmaniasis (VL) is a severe and potentially fatal neglected tropical disease, being considered a public health concern in many countries worldwide. There are still no vaccines against human VL, and the existing chemotherapy is often toxic. Thereby, alternative treatments have been investigated, and byproducts from plant metabolism have been a source of promising pharmacological compounds. Terpenes are secondary metabolites that exhibit a large spectrum of therapeutic activities. Herein, we conducted a systematic review to evaluate the effects of terpenes in the treatment of VL in rodents. After an extensive search using the PubMed/MEDLINE, Scopus, and Web of Science databases, we included 34 articles in this review. Our results revealed that triterpenes were the most used terpenes by the eligible studies. Overall, terpene treatment showed no or negligible toxicity, causing an increase in the Th1-type immune response profile and nitric oxide production. It also reduced the Th2 cytokines levels and parasite load (> 90% to > 99%). Moreover, terpenes induced apoptosis by damaging the plasma membrane and inhibiting DNA topoisomerases in the parasite. The use of terpene carriers increased the terpene bioavailability in the body, preventing their rapid excretion and promoting the drug delivery at the site of Leishmania infection. Terpene derivatives showed better pharmacokinetics than the original terpenes. Altogether, the benefits of VL treatment with terpenes in preclinical studies may open new directions for other preclinical and human trials.


Assuntos
Leishmaniose Visceral , Triterpenos , Sistemas de Liberação de Medicamentos , Humanos , Leishmaniose Visceral/tratamento farmacológico , Fitoterapia , Terpenos/farmacologia , Terpenos/uso terapêutico
4.
Andrologia ; 54(11): e14615, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36261879

RESUMO

Seminal plasma is a dynamic, intricate combination of fluids from the testicles, epididymides, seminal vesicles, bulbourethral glands, and prostate, containing molecules that modulate sperm functions, post-fertilization events, and the female reproductive tract physiology. Significant variations in sperm parameters and fertility status of bulls relate to differences in the seminal plasma proteome. In this framework, a meta-analytical study was conducted examining 29 studies (published between 1990 and 2021) to ascertain the effects of seminal fluid proteins on parameters associated with bull fertility and the influence of distinct methodologies on such effects. Our results revealed that seminal proteins ameliorate sperm parameters, such as motility, integrity, capacitation, and fertilizing ability, and favours sperm protection. Seminal binder of sperm proteins and beta-defensin 126 highly favoured sperm protection when cells were collected from the epididymis by retrograde flux and analysed under room temperature conditions. Furthermore, seminal proteins improved the motility and quality of Bos taurus sperm collected by artificial vagina, mainly in the presence of heparin-binding proteins. The key limitations faced by this meta-analysis were the paucity of studies evaluating the effects of whole seminal fluid proteins and the limited number of studies conducted in vivo. In conclusion, the present meta-analytical study confirms that seminal proteins improve fertility-related parameters in the bovine species. However, methodological strategies used by authors are diverse, with distinct endpoints and methods. Thus, the translational aspects of seminal plasma research should be taken into consideration to precisely define how seminal proteins can be harnessed to advance reproductive biotechnology.


Assuntos
Sêmen , Proteínas de Plasma Seminal , Bovinos , Masculino , Animais , Feminino , Proteínas de Plasma Seminal/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Fertilização , Fertilidade/fisiologia
5.
Reproduction ; 161(4): 459-475, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33606662

RESUMO

Proteomic approaches have been widely used in reproductive studies to uncover protein biomarkers of bull fertility. Seminal plasma is one of the most relevant sources of these proteins that may influence sperm physiology. Nonetheless, there are still gaps in existing knowledge in the functional attributes of seminal proteins. Thus, we reviewed the relationships between seminal plasma proteins and bull fertility by conducting a systematic review with data obtained from 71 studies. This review showed that the associations related to fertility improvement with the use of total seminal plasma proteins are still controversial. None of the studies explored the sperm fertilizing ability following these interactions. By contrast, the exposure to a single protein, such as osteopontin, binder of sperm proteins, and heparin binding proteins, can increment sperm motility, capacitation, and fertilizing ability by modulating intracellular calcium concentrations, removing lipids from sperm membranes, and regulating the acrosome reaction. Variations in protein analyses and the protein contents and their abundances between animals contributed to the difficulty of establishing protein biomarkers of fertilizing potential of the bull sperm. Indeed, the heterogenicity of methodologies was a limitation of this review. Standardized methods of seminal protein analyses, as well as sperm endpoints, may minimize such discrepancies. In conclusion, potential biomarkers of sperm parameters are still to be established. Future studies should evaluate protein isoforms and how they interact with sperm to ascertain their biological functions.


Assuntos
Fertilidade , Reprodução , Proteínas de Plasma Seminal/metabolismo , Animais , Bovinos , Masculino
6.
Pharmacol Res ; 165: 105315, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33497803

RESUMO

Diabetes is a highly prevalent health condition affecting many people worldwide. In vitro studies have described the positive effects of cloves and its major compound, eugenol, in the treatment of diabetes. However, it is unclear whether the effects of this compound are negative, neutral, or positive, on hyperglycemic animals. Therefore, a meta-analytical review was conducted to determine the magnitude of effects of eugenol on variables directly and indirectly related to diabetes. This study revealed that eugenol treatment decreased the glucose levels and the activity of carbohydrate-metabolizing enzymes, ameliorated the lipid profile, and reduced the oxidative, renal, and hepatic damages in hyperglycemic rodents. Moreover, eugenol alleviated the weight loss and restored the activity of the antioxidant defense system. Insulin levels was not affected by eugenol treatment. Also, mixed model analyses revealed that the use of purified or non-purified eugenol and the concentrations administered significantly affected the treatment outcome. In conclusion, our findings indicate that eugenol may have potential therapeutic effects in the treatment of diabetes. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Eugenol/uso terapêutico , Hipoglicemiantes/uso terapêutico , Animais , Feminino , Hiperglicemia/tratamento farmacológico , Camundongos , Gravidez , Ratos
7.
Microsc Microanal ; : 1-13, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34184626

RESUMO

Green tea is a popular drink used for therapeutic purposes to mitigate the consequences of diabetes. In this study, we aimed at evaluating the potential of green tea infusion to ameliorate structural and enzymatic damages caused by hyperglycemia in the testis and epididymis of Wistar rats. For that, nondiabetic and streptozotocin-induced diabetic rats (negative control and diabetes control, respectively) received 0.6 mL of water by gavage. Another set of diabetic animals received 100 mg/kg of green tea infusion diluted in 0.6 mL of water/gavage (diabetes + green tea) daily. After 42 days of treatment, the testes and epididymides were removed and processed for histopathological analysis, micromineral determination, and enzymatic assays. The results showed that treatment with green tea infusion preserved the testicular and epididymal histoarchitecture, improving the seminiferous epithelium and the sperm production previously affected by diabetes. Treatment with green tea reduced tissue damages caused by this metabolic condition. Given the severity of hyperglycemia, there was no efficacy of the green tea infusion in maintaining the testosterone levels, antioxidant enzyme activity, and microminerals content. Thus, our findings indicate a protective effect of this infusion on histological parameters, with possible use as a complementary therapy for diabetes.

8.
Int J Exp Pathol ; 101(3-4): 106-121, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32452573

RESUMO

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MSn ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Florestas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanaceae/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Células MCF-7 , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química
9.
Toxicol Appl Pharmacol ; 409: 115304, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33127376

RESUMO

Arsenic induces reproductive disorders in pubertal males after prepubertal exposure. However, it is unclear the extent to which those effects remain in testis and epididymis of sexually mature rats after arsenic insult. This study evaluated the effects of prepubertal arsenic exposure in male organs of pubertal rats, and their reversibility in adult rats. Male pups of Wistar rats on postnatal day (PND) 21 were divided into two groups (n = 20/group): Control animals received filtered water and exposed rats received 10 mg L--1 arsenic from PND 21 to PND 51. At PND 52, testis and epididymis of ten animals per group were examined for toxic effects under morphological, functional, and molecular approaches. The other animals were kept alive under free arsenic conditions until PND 82, and further analyzed for the same parameters. Pubertal rats overexpressed mRNA levels of SOD1, SOD2, CAT, GSTK1, and MT1 in their testis and SOD1, CAT, and GSTK1 in their epididymis. In those organs, catalase activity was altered, generating byproducts of oxidative stress. The antioxidant gene expression was unchanged in adult rats in contrast to the altered activity of antioxidant enzymes. Histological alterations of testis and epididymis tissues were observed in pubertal and adult rats. Interestingly, only adult rats exhibited a remarkable decrease in serum testosterone levels. Prepubertal exposure to arsenic caused morphological and functional alterations in male reproductive organs of pubertal rats. In adult rats, these damages disappeared, remained, get worsened, or recovered depending on the parameter analyzed, indicating potential male fertility disorders during adulthood.


Assuntos
Arsênio/toxicidade , Reprodução/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
10.
Anticancer Drugs ; 31(7): 718-727, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32568827

RESUMO

Conventional treatments for metastatic melanomas are still ineffective and generate numerous side effects, justifying the search for new therapies. The antimetastatic effect of the named N-(2-(4-bromophenylamino)-5-(trifluoromethyl)phenyl)nicotinamide (SRVIC30) compound has been previously demonstrated in murine melanoma. Herein, we aimed to evaluate its effect when topically administrated in a murine subcutaneous melanoma model. For that, mice C57BL/6 were injected subcutaneously with 2 × 10 B16-F10 cells. Topical treatment began when tumors became visible on animal's back. Therefore, tumor volume was measured three times a week until it reaches 12 mm approximately. At this point, 40 mg oil-in-water cream (Lanette) without (control mice; n = 10) or with SRVIC30 compound (SRVIC30 group; n = 10 animals) were spread daily over the tumor external surface using a small brush for 14 days. The treatments increased the percentage of peroxidase antioxidant enzyme and dead cells via caspase-3 activation, with a consequent deposit of collagen fibers in the tumors. In addition, the skin of treated animals showed the presence of inflammatory infiltrate. Finally, SRVIC30 did not show signs of toxicity. Thus, we concluded that the topic administration of SRVIC30 was able to influence crucial anticancer processes such as tumor cells apoptosis and surrounding microenvironment.


Assuntos
Melanoma Experimental/tratamento farmacológico , Niacinamida/análogos & derivados , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Animais , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Neoplasias Cutâneas/patologia
11.
J Appl Toxicol ; 40(2): 214-223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31429093

RESUMO

Arsenic is a metalloid widely found in the environment in organic and inorganic forms. Exposure to inorganic arsenic forms via drinking water has been associated with an increased incidence of negative health effects, including reproductive disorders and dysfunction of the endocrine system. However, the impact of arsenic exposure on female reproductive development is still unclear. Therefore, in the present study, we evaluated the effects of prenatal exposure to arsenic on the initial sexual development and puberty onset, and in the morphology of the female reproductive organs, estrous cycle regularity and fertility parameters during adulthood. To do that, pregnant female Wistar rats were exposed to 10 mg/L sodium arsenite via drinking water from gestational day (GD) 1 until GD 21 and the female offspring was evaluated in different postnatal days. Our results showed that prenatal arsenic exposure induced a decrease of litter weight and morphological masculinization in females at postnatal day 1. Moreover, these females had a delay in the age of puberty onset and alteration in estrous cycle number and length. During adulthood, females from the sodium arsenite group showed an increase in endometrium, myometrium and perimetrium areas, and an imbalance in uterine antioxidant enzyme activity. These animals also presented an increase in post-implantation loss and reabsorption number, leading to reduced viable fetus number. In conclusion, prenatal arsenic exposure in rats was able to promote female masculinization, alter sexual development and impair reproductive performance.


Assuntos
Arsenitos/toxicidade , Ciclo Estral/efeitos dos fármacos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Puberdade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Compostos de Sódio/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Modelos Animais , Gravidez , Ratos , Ratos Wistar
12.
Gen Comp Endocrinol ; 273: 32-39, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29574151

RESUMO

Chinchilla lanigera is a hystricomorph rodent from South America whose reproductive biology presents particular characteristics that distinguishes it from other Rodentia species, such as low reproductive rate, seasonal breeding pattern, and long estrous cycle. Nevertheless, reproductive features in female chinchillas are still poorly investigated, with a scarce knowledge concerning the estrous cycle and the histology of reproductive organs. In this study, we investigate the morphology, histomorphometry, secretory activity, and immunolocalization of estrogen receptors ERα and ERß in oviducts of nulliparous chinchillas, euthanized at fall season in Brazil. Follicular phase of estrous cycle of all studied animals was characterized by ovary and uterine morphology inspection, as well as vaginal cytology. Similar to other mammals, the oviduct wall of infundibulum, ampulla and isthmus was composed of mucosa, muscle, and serosa layers. Morphometric data of oviduct layers were used for identifying each oviduct segment. In the follicular phase, the oviduct was characterized by intense secretory activity, mainly in the ampulla, and expression of ERα and ERß throughout the oviduct epithelium. Both ERα and ERß were also detected in the connective tissue and smooth muscle cells. Our findings point out to the important role of estrogen in this female organ. Similar wide distribution of both ER proteins has been described for human Fallopian tube. Taken together, our data add to the understanding of the reproductive biology of female chinchillas, and may assist in the intensive breeding of this species and any eventual endeavor for conservation of chinchillas in the wild.


Assuntos
Chinchila/anatomia & histologia , Chinchila/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Oviductos/anatomia & histologia , Oviductos/metabolismo , Animais , Especificidade de Anticorpos , Endométrio/citologia , Epitélio/metabolismo , Feminino , Ovário/citologia , Ovário/metabolismo , Vagina/citologia , Vagina/metabolismo
13.
Reprod Domest Anim ; 54(7): 939-948, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30246506

RESUMO

Brazilian Somalis is a locally-adapted breed of rams raised in tropical climate and native pastures. The present study was conducted to evaluate gene expression and proteome of the reproductive tract of such rams. Samples were collected from testes, epididymides, seminal vesicles and bulbourethral glands of four rams. Expression of clusterin (CLU), osteopontin (OPN) and prostaglandin D2 synthase (PGDS) genes were evaluated in all samples by real-time PCR. Shotgun proteomic analysis was performed using samples from the head, corpus and cauda epididymides and from all other structures as well. Gene ontology terms and protein interactions were obtained from UniProtKB databases and MetaCore v.6.8 platform. CLU trasncripts were detected in the testes, epididymides, seminal vesicles and bulbourethral glands of the Somalis rams. The initial region and body of the epididymis had the greatest CLU expression. OPN mRNA was localized in all tissues of the ram reproductive tract. PGDS mRNA was detected in the testes and epididymides. Lable-free mass spectrometry allowed the identification of 137 proteins in all samples. Proteins of the epididymis head mainly participate in cellular processes and response to stimulus, participating in catalityc activity and binding. Proteins of epididymis body acted as regulatory proteins and in cellular processes, with binding and catalytic activity. Cauda epididymis molecules were associated with cellular processes and regulation, with binding function and catalytic activity as well. Testis proteins were mainly linked to cell processes and response to stimuli, and had catalytic function. Seminal vesicle proteins were involved in regulation and mainly with binding functions. Most bulbourethral gland proteins participated in cellular processes. The present study is the first to evaluate the proteome and gene expressions in the reproductive tract of Brazilian Somalis rams. Such pieces of information bring significant cointribution for the understanding of the reproductive physiology of locally-adapted livestock.


Assuntos
Genitália Masculina/metabolismo , Proteoma/análise , Carneiro Doméstico/genética , Carneiro Doméstico/metabolismo , Adaptação Fisiológica , Animais , Brasil , Clusterina/genética , Clusterina/metabolismo , Expressão Gênica , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/genética , Lipocalinas/metabolismo , Masculino , Osteopontina/genética , Osteopontina/metabolismo , Clima Tropical
14.
Cell Tissue Res ; 372(1): 135-147, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29119327

RESUMO

In the epididymis, epithelial cells work in a concerted manner to create a luminal environment for sperm maturation, transport, and storage. However, the cell functions may be affected by anthropogenic factors, causing negative impacts on male fertility. In our study, we describe the pattern of protein expression in the epithelium and luminal fluid from epididymis of Oligoryzomys nigripes, a South American sigmodontine rodent whose reproductive biology has been little studied. Nine animals were captured from a preserved area of Atlantic Forest, where the exposure to anthropogenic influences is minimal. Epididymides were processed for histological analysis under light and epifluorescence microscopy, in which we used cell-specific markers aquaporin 9 (AQP9), vacuolar H+-ATPase (V-ATPase), and cytokeratin 5 (KRT5). Other samples were assessed for protein expression using shotgun proteomics. Similar to laboratory rodents, principal cells expressed AQP9 in their stereocilia. Basal cells, identified by KRT5 labeling, presented lateral body projections and a few axiopodia going toward the lumen. Clear cells expressed V-ATPase in their sub-apical vesicles and microplicae, and showed different shapes along the duct. Shotgun proteomics detected 51 proteins from epididymal supernatant. Most of them have been previously described in other species, indicating that they are well conserved. Twenty-three proteins detected in O. nigripes have not been described in epididymis from other South American sigmodontine rodents, confirming that the secretion pattern is species-specific. Our findings in O. nigripes from a protected area may help to create a baseline for studies investigating the effects of anthropogenic factors on functionality of the epididymal epithelium.


Assuntos
Epididimo/metabolismo , Proteínas/metabolismo , Sigmodontinae/metabolismo , Animais , Epididimo/anatomia & histologia , Epididimo/citologia , Ontologia Genética , Imageamento Tridimensional , Masculino , Anotação de Sequência Molecular , Proteômica
15.
Toxicol Appl Pharmacol ; 356: 214-223, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30138656

RESUMO

The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers.


Assuntos
Antineoplásicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Ensaio Tumoral de Célula-Tronco
16.
Bull Environ Contam Toxicol ; 101(2): 197-204, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29881942

RESUMO

This study evaluated the effects of a commercially recommended concentration (1 mL/L) of a fungicide tebuconazole (TBZ) on testicular and epididymal histomorphometry of Artibeus lituratus, following 7 and 30-day oral exposure. TBZ30 bats showed a reduction in the percentage of tubules and seminiferous epithelium, as well as a decrease in tubule and epithelium somatic indexes, and tubular diameter. Inversely, these animals showed increased percentage of intertubular compartment, Leydig cells and blood vessels. The volume of Leydig cells and their number per gram of testis also increased in TBZ30 bats. Alterations in epididymal morphometry were observed in all regions of the organ, with increase of ductal diameter in both exposure times. These results indicate that exposure to low concentration of TBZ resulted in testicular and epididymal morphometric changes in fruit bats, mainly at 30-day exposure, suggesting that functional alterations might be occurring in these organs and impacting reproductive capacity.


Assuntos
Exposição Dietética/efeitos adversos , Fungicidas Industriais/toxicidade , Testículo/efeitos dos fármacos , Triazóis/toxicidade , Animais , Quirópteros , Masculino , Reprodução/efeitos dos fármacos
17.
Histochem Cell Biol ; 147(1): 39-48, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27549752

RESUMO

Desmodus rotundus is a vampire bat species that inhabits Latin America. Some basic aspects of this species' biology are still unknown, as the histophysiological characteristics of the male reproductive tract. Our study has focused on its epididymis, which is an important organ for performing a variety of functions, especially the sperm maturation and storage. The aim of this study was to identify principal, narrow, clear, and basal cells using cell-specific markers such as aquaporin 9 (AQP9), vacuolar H+-ATPase (V-ATPase), and cytokeratin 5 (KRT5). Principal cells were labeled by AQP9 from initial segment to cauda region in their stereocilia. They were shown with a columnar shape, whereas V-ATPase-rich cells were identified with a goblet-shaped body along the entire epididymis, including the initial segment, which were named as clear cells. Pencil-shaped V-ATPase-rich cells (narrow cells) were not detected in the initial segment of the bat epididymis, unlike in the rodent. Basal cells were labeled by KRT5 and were located at the basal portion of the epithelium forming a dense network. However, no basal cells with a luminal-reaching body extension were observed in the bat epididymis. In summary, epithelial cells were identified by their specific markers in the vampire bat epididymis. Principal and basal cells were labeled by AQP9 and KRT5, respectively. Narrow cells were not observed in the vampire bat epididymis, whereas clear cells were identified by V-ATPase labeling along the entire duct in a goblet-shaped body. In addition, no luminal-reaching basal cells were observed in the vampire bat epididymis.


Assuntos
Aquaporinas/metabolismo , Epididimo/metabolismo , Queratina-5/biossíntese , Queratina-5/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Aquaporinas/análise , Aquaporinas/biossíntese , Quirópteros , Epididimo/citologia , Imunofluorescência , Queratina-5/análise , Masculino , Microscopia Eletrônica de Transmissão , ATPases Vacuolares Próton-Translocadoras/análise , ATPases Vacuolares Próton-Translocadoras/biossíntese
18.
J Toxicol Environ Health A ; 79(6): 274-86, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27029432

RESUMO

Arsenic (As), in the form of trivalent arsenite or pentavalent arsenate, is a ubiquitous toxic compound naturally occurring in the environment. This study aimed to evaluate the impact of two different forms of inorganic As on reproductive parameters following oral exposure. Adult Wistar male rats were exposed to sodium arsenite or arsenate at concentrations of 0.01 mg/L or 10 mg/L for 56 d in drinking water. Sodium arsenite at both concentrations and sodium arsenate at 10 mg/L produced reduction in daily sperm production, in number of spermatids in the testis, and in sperm in the epididymal caput/corpus regions. Changes in epididymal morphometry were variable and region specific. Total and progressive sperm motility and sperm morphology did not differ markedly between controls and animals exposed to As. The body and reproductive organs weights, as well as testosterone concentration, remained unchanged among all groups. In conclusion, As exposure in drinking water over 56 d produced damage in male reproductive functions in adult rats, suggesting that fertility problems might occur. Therefore, additional studies need to be undertaken to investigate potential mechanisms underlying sodium arsenite- and arsenate-induced disturbances in fertility and reproductive performance.


Assuntos
Arseniatos/toxicidade , Arsenitos/toxicidade , Fertilidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Água Potável , Epididimo/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestrutura , Testosterona/metabolismo
19.
Theriogenology ; 222: 31-44, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615434

RESUMO

There is still no consensus regarding the role of lipid modulators during in vitro embryo production. Thus, we investigated how lipid reducers during the in vitro maturation of oocytes (IVM) or in vitro culture (IVC) of embryos impact their cryotolerance. A literature search was performed using three databases, recovering 43 articles for the systematic review, comprising 75 experiments (13 performed in IVM, 62 in IVC) and testing 13 substances. In 39 % of the experiments, an increase in oocyte and/or embryo survival after cryopreservation was reported, in contrast to 48 % exhibiting no effect, 5 % causing negative effects, and 8 % influencing in a dose-dependent manner. Of the 75 experiments extracted during IVM and IVC, 41 quantified the lipid content. Of those that reduced lipid content (n = 26), 50 % increased cryotolerance, 34 % had no effect, 8 % harmed oocyte/embryo survival, and 8 % had different results depending on the concentration used. Moreover, 28 out of the 43 studies were analyzed under a meta-analytical approach at the IVC stage in cattle. There was an improvement in the cryotolerance of bovine embryos when the lipid content was reduced. Forskolin, l-carnitine, and phenazine ethosulfate positively affected cryotolerance, while conjugated linoleic acid had no effect and impaired embryonic development. Moreover, fetal bovine serum has a positive impact on cryotolerance. SOF and CR1aa IVC media improved cryotolerance, while mSOF showed no effect. In conclusion, lipid modulators did not unanimously improve cryotolerance, especially when used in IVM, but presented positive effects on cryotolerance during IVC when reaching lipid reduction.


Assuntos
Criopreservação , Técnicas de Cultura Embrionária , Animais , Criopreservação/veterinária , Criopreservação/métodos , Técnicas de Cultura Embrionária/veterinária , Lipídeos/química , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Fertilização in vitro/veterinária , Bovinos/embriologia , Metabolismo dos Lipídeos , Embrião de Mamíferos/fisiologia
20.
Biol Trace Elem Res ; 202(4): 1644-1655, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37495827

RESUMO

This study evaluated the effect of prepubertal arsenic exposure in the liver and kidney of pubescent rats and their reversibility 30 days after arsenic withdrawal. Male pups of Wistar rats (21 days old) were divided into two groups (n = 20/group): control animals received filtered water, and exposed rats received 10 mg L-1 arsenic from postnatal day (PND) 21 to PND 51. The liver and kidney of 52 days old rats (n = 10/group) were examined to investigate the effects of arsenic on micromineral content, antioxidant enzyme activity, histology, and biochemistry parameters. The other animals were kept alive under free arsenic conditions until 82 days old and further analyzed by the same parameters. Our results revealed that 52-day-old rats increased arsenic content in their liver and arsenic and manganese in their kidney. In those animals, glycogen and zinc content and catalase activity were reduced in the liver, and the selenium content decreased in the kidney. Thirty days later, arsenic reduced the manganese and iron content and SOD and CAT activity in the liver of 82-day-old rats previously exposed to arsenic, while glycogen and selenium content decreased in their kidney. In contrast, PND 82 rats exhibited higher retention of copper in the liver, an increase in iron and copper content, and CAT and GST activity in the kidney. Significant histological alterations of liver and kidney tissues were not observed in rats of both ages. We conclude that arsenic-induced toxicity could alter differently the oxidative status and balance of trace elements in pubertal and adult rats, demonstrating that the metalloid can cause effects in adulthood.


Assuntos
Arsênio , Selênio , Ratos , Masculino , Animais , Arsênio/metabolismo , Cobre/farmacologia , Ratos Wistar , Selênio/farmacologia , Selênio/metabolismo , Manganês/farmacologia , Catalase/metabolismo , Antioxidantes/metabolismo , Fígado/metabolismo , Rim/metabolismo , Ferro/metabolismo , Estresse Oxidativo , Glicogênio/metabolismo
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