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1.
Environ Pollut ; 284: 117518, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261222

RESUMO

Perfluorooctane sulfonate (PFOS), an artificial perfluorinated compound, has been associated with male reproductive disorders. Histone modifications are important epigenetic mediators; however, the impact of PFOS exposure on testicular steroidogenesis through histone modification regulations remains to be elucidated. In this study, we examined the roles of histone modifications in regulating steroid hormone production in male rats chronically exposed to low-level PFOS. The results indicate that PFOS exposure significantly up-regulated the expressions of StAR, CYP11A1 and 3ß-HSD, while CYP17A1 and 17ß-HSD were down-regulated, thus contributing to the elevated progesterone and testosterone levels. Furthermore, PFOS significantly increased the histones H3K9me2, H3K9ac and H3K18ac while reduced H3K9me3 in rat testis. It is known that histone modifications are closely involved in gene transcription. Therefore, to investigate the association between histone modifications and steroidogenic gene regulation, the levels of these histone marks were further measured in steroidogenic gene promoter regions by ChIP. It was found that H3K18ac was augmented in Cyp11a1 promoter, and H3K9ac was increased in Hsd3b after PFOS exposure, which is proposed to result in the activation of CYP11A1 and 3ß-HSD, respectively. To sum up, chronic low-level PFOS exposure activated key steroidogenic gene expression through enhancing histone acetylation (H3K9ac and H3K18ac), ultimately stimulating steroid hormone biosynthesis in rat testis.


Assuntos
Histonas , Testículo , Acetilação , Ácidos Alcanossulfônicos , Animais , Fluorcarbonetos , Histonas/metabolismo , Masculino , Ratos , Testículo/metabolismo , Testosterona/metabolismo
2.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198754

RESUMO

BACKGROUND: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Parquetina nigrescens (HELEPN) against d-galactose-induced testicular injury. METHODS: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. RESULTS: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. CONCLUSION: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.


Assuntos
Apocynaceae/química , Galactose/efeitos adversos , Infertilidade Masculina/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Testículo/lesões , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Gonadotropinas/metabolismo , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Distribuição Aleatória , Ratos , Ratos Wistar , Análise do Sêmen , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
3.
Womens Health (Lond) ; 17: 17455065211022262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34096383

RESUMO

In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.


Assuntos
Envelhecimento/imunologia , COVID-19/imunologia , Sistema Imunitário/fisiologia , Imunidade/fisiologia , Fatores Sexuais , Estrogênios/metabolismo , Feminino , Humanos , Masculino , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Testosterona/metabolismo , Vacinação
4.
Life Sci ; 278: 119570, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33964295

RESUMO

AIMS: Increasing evidence has shown that hormone secretion is regulated by endocytosis. Eps15 homology domain-containing protein 3 (EHD3) is an endocytic-trafficking regulatory protein, but whether EHD3 is associated with testosterone secretion is not clear. This work aims to explore the role of EHD3 in testosterone synthesis. MAIN METHODS: Testosterone concentration was determined by ELISA. The effects of EHD3 on endocytosis were assessed by exosomes tracing assay and Immunofluorescence. Targeting relationship between EHD3 and NR5A1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assay in Leydig cells. For in vivo assessments, conditional NR5A1 knockout mouse model was established with CRISPR/Cas9 gene targeting technology. KEY FINDINGS: EHD3 overexpression significantly increased the concentration of testosterone. EHD3 knockdown markedly decreased testosterone synthesis by reducing endocytosis. The activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence "AGGTCA" in the EHD3 promoter. Furthermore, mice with a Leydig cell-specific conditional NR5A1 knockout displayed the blunted levels of EHD3 and clathrin (a key factor for endocytosis), and serum testosterone concentration compared with NR5A1f/f mice. SIGNIFICANCE: This study suggests a potential molecular mechanism of testosterone synthesis to fully understand male reproductive health.


Assuntos
Proteínas de Transporte/metabolismo , Endocitose , Exossomos/metabolismo , Regulação da Expressão Gênica , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismo , Animais , Sistemas CRISPR-Cas , Proteínas de Transporte/genética , Imunoprecipitação da Cromatina , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , RNA Interferente Pequeno/metabolismo , Fator Esteroidogênico 1/genética , Testosterona/farmacologia
5.
Nat Commun ; 12(1): 2496, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941789

RESUMO

Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3ß/ß-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.


Assuntos
Núcleo Central da Amígdala/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Consolidação da Memória/fisiologia , Precursores de Proteínas/antagonistas & inibidores , Taquicininas/antagonistas & inibidores , Animais , Antipsicóticos/farmacologia , Estradiol/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/farmacologia , Precursores de Proteínas/metabolismo , Fatores Sexuais , Transdução de Sinais , Taquicininas/metabolismo , Testosterona/metabolismo
6.
Aquat Toxicol ; 235: 105819, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33873058

RESUMO

Despite of physiological and toxicological relevance, the potential of androgens to influence fish lipid metabolism remains poorly explored. Here, brown trout primary hepatocytes were exposed to six concentrations (1 nM to 100 µM) of dihydrotestosterone (DHT) and testosterone (T), to assess changes in the mRNA levels of genes covering diverse lipid metabolic pathways. Acsl1, essential for fatty acid activation, was up-regulated by T and DHT, whereas the lipogenic enzymes FAS and ACC were up-regulated by the highest (100 µM) concentration of T and DHT, respectively. ApoA1, the major component of high-density lipoprotein (HDL), was down-regulated by both androgens. PPARγ, linked to adipogenesis and peroxisomal ß-oxidation, was down-regulated by T and DHT, while Acox1-3I, rate-limiting in peroxisomal ß-oxidation, was down-regulated by T. Fabp1, StAR and LPL were not altered. Our findings suggest that androgens may impact on lipid transport, adipogenesis and fatty acid ß-oxidation and promote lipogenesis in fish liver.


Assuntos
Di-Hidrotestosterona/metabolismo , Testosterona/metabolismo , Truta/fisiologia , Poluentes Químicos da Água/metabolismo , Androgênios/metabolismo , Androgênios/toxicidade , Animais , Di-Hidrotestosterona/toxicidade , Proteínas de Ligação a Ácido Graxo , Ácidos Graxos/metabolismo , Hepatócitos/metabolismo , Hepatócitos/fisiologia , Metabolismo dos Lipídeos , Lipogênese , Fígado/metabolismo , PPAR gama/metabolismo , Testosterona/toxicidade , Truta/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Int J Nanomedicine ; 16: 2555-2568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833511

RESUMO

Introduction: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects. Methods: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days. Results: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.


Assuntos
Infertilidade Masculina/prevenção & controle , Nanopartículas Metálicas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Reprodução , Prata/toxicidade , Testículo/efeitos dos fármacos , Zinco/farmacologia , Animais , Antioxidantes/farmacologia , Infertilidade Masculina/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Ratos , Ratos Sprague-Dawley , Motilidade Espermática/efeitos dos fármacos , Testosterona/metabolismo
8.
Molecules ; 26(6)2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33799482

RESUMO

Flavonoids are plant bioactives that are recognized as hormone-like polyphenols because of their similarity to the endogenous sex steroids 17ß-estradiol and testosterone, and to their estrogen- and androgen-like activity. Most efforts to verify flavonoid binding to nuclear receptors (NRs) and explain their action have been focused on ERα, while less attention has been paid to other nuclear and non-nuclear membrane androgen and estrogen receptors. Here, we investigate six flavonoids (apigenin, genistein, luteolin, naringenin, quercetin, and resveratrol) that are widely present in fruits and vegetables, and often used as replacement therapy in menopause. We performed comparative computational docking simulations to predict their capability of binding nuclear receptors ERα, ERß, ERRß, ERRγ, androgen receptor (AR), and its variant ART877A and membrane receptors for androgens, i.e., ZIP9, GPRC6A, OXER1, TRPM8, and estrogens, i.e., G Protein-Coupled Estrogen Receptor (GPER). In agreement with data reported in literature, our results suggest that these flavonoids show a relevant degree of complementarity with both estrogen and androgen NR binding sites, likely triggering genomic-mediated effects. It is noteworthy that reliable protein-ligand complexes and estimated interaction energies were also obtained for some suggested estrogen and androgen membrane receptors, indicating that flavonoids could also exert non-genomic actions. Further investigations are needed to clarify flavonoid multiple genomic and non-genomic effects. Caution in their administration could be necessary, until the safe assumption of these natural molecules that are largely present in food is assured.


Assuntos
Androgênios/metabolismo , Núcleo Celular/metabolismo , Estrogênios/metabolismo , Flavonoides/metabolismo , Ligação Proteica/fisiologia , Receptores de Superfície Celular/metabolismo , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Simulação de Acoplamento Molecular , Receptores de Estrogênio , Testosterona/metabolismo
9.
Front Endocrinol (Lausanne) ; 12: 607179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796068

RESUMO

COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve. In this mini-review, we focus on the role of testosterone through a discussion of the intricate mechanisms of disease development and deterioration. Accumulated evidence suggests that there are links between high level (normal male level) as well as low level (age-related hypogonadism) testosterone in disease progression and expansion, supporting its role as a double-edged sword. Unresolved questions point to the essential need for further targeted studies to substantiate these contrasting mechanisms.


Assuntos
COVID-19/metabolismo , Pandemias , Testosterona/metabolismo , COVID-19/complicações , COVID-19/tratamento farmacológico , Feminino , Humanos , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Masculino , Testosterona/uso terapêutico
10.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802611

RESUMO

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3ß-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell-cell junction genes (i.e., zonula occcludens protein-1, vimentin and ß-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/metabolismo , Endocanabinoides/metabolismo , Epididimo/efeitos dos fármacos , Estrogênios/metabolismo , Células Germinativas/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/metabolismo , Tecido Adiposo/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Epididimo/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Células Germinativas/metabolismo , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Masculino , Camundongos , Fatores de Risco , Testosterona/metabolismo
11.
Biochem Biophys Res Commun ; 551: 54-62, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33721831

RESUMO

Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high sociality, we cloned and characterized some sociality-related genes of degus, in order to establish degus as a highly socialized animal model in molecular biology. We cloned degus Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. According to our results, amino acid sequences of Neurexin and Neuroligin expressed in degus brain, are highly conserved to that of human sequences. Most notably, degus Neuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated that degus has the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Octodon/metabolismo , Receptores de Superfície Celular/metabolismo , Testosterona/metabolismo , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Proteínas de Ligação ao Cálcio/química , Moléculas de Adesão Celular Neuronais/química , Moléculas de Adesão Celular Neuronais/genética , Hipocampo/metabolismo , Humanos , Masculino , Moléculas de Adesão de Célula Nervosa/química , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos , Receptores de Superfície Celular/química , Globulina de Ligação a Hormônio Sexual/química , Testosterona/farmacologia
12.
Andrologia ; 53(5): e14037, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33724529

RESUMO

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p < .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.


Assuntos
Acetilcisteína , Fluorcarbonetos , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Caprilatos , Fluorcarbonetos/metabolismo , Fluorcarbonetos/toxicidade , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Motilidade Espermática , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
13.
Andrologia ; 53(6): e14045, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33769572

RESUMO

This study explored treatment with Taif rosewater (RW) to protect against lead acetate-(PbAc) induced male testicular impairment. Male Wistar rats were divided into four groups and provided drinking water containing 4% Taif RW, PbAc, 4% Taif RW followed by PbAc or normal water (controls). Serum for hormonal assays and testicular tissue for histopathological and immunohistochemical examinations and molecular study were obtained. Epididymal spermatozoa were collected for analysis. PbAc significantly reduced serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone, as well as sperm count and motility percentage. It also caused a significant reduction in SOD and catalase activities, testicular CYTP450SCC , CYP17α, StAR mRNA expressions and the percentage of Bcl-2 immunoreactivity. The percentage of caspase-3 and NF-ĸB immunoreactivities, as well as sperm abnormalities, was increased, as did the testicular degeneration associated with vacuolation and necrosis of spermatogenic cells. Pretreatment with Taif RW significantly reduced the negative effects of PbAc as shown by the increases in serum gonadotropins level, SOD and catalase activities, and percentage of Bcl-2 immunoreactivity, decreases in the percentage of caspase-3 and NF-ĸB immunoreactivities, and improved testicular histology and sperm parameters. These data provide evidence that Taif RW protects against testicular toxicity caused by PbAc.


Assuntos
Espermatozoides , Testículo , Animais , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática , Testículo/metabolismo , Testosterona/metabolismo
14.
Eur J Pharmacol ; 899: 173998, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33676942

RESUMO

Various antidepressants are commonly used to treat depression and anxiety disorders, and sex differences have been identified in their efficacy and side effects. Steroids, such as estrogens and testosterone, both in the periphery and locally in the brain, are regarded as important modulators of these sex differences. This review presents published data from preclinical and clinical studies that measure testosterone and estrogen level changes during and/or after acute or chronic administration of different antidepressants. The majority of studies show an interaction between sex hormones and antidepressants on sexual function and behavior, or in depressive symptom alleviation. However, most of the studies omit to investigate antidepressants' effects on circulating levels of gonadal hormones. From data reviewed herein, it is evident that most antidepressants can influence testosterone and estrogen levels. Still, the evidence is conflicting with some studies showing an increase, others decrease or no effect. Most studies are conducted in male animals or humans, underscoring the importance of considering sex as an important variable in such investigations, especially as depression and anxiety disorders are more common in women than men. Therefore, research is needed to elucidate the extent to which antidepressants can influence both peripheral and brain levels of testosterone and estrogens, in males and females, and whether this impacts the effectiveness or side effects of antidepressants.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos/uso terapêutico , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Estrogênios/metabolismo , Testosterona/metabolismo , Animais , Antidepressivos/efeitos adversos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Depressão/metabolismo , Depressão/fisiopatologia , Depressão/psicologia , Estrogênios/sangue , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco , Fatores Sexuais , Testosterona/sangue , Resultado do Tratamento
15.
Environ Toxicol ; 36(6): 1206-1216, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33683001

RESUMO

Perfluorotridecanoic acid (PFTrDA) is a long-chain perfluoroalkyl substance, and its effect on the differentiation of fetal Leydig cells remains unclear. The objective of this study is to explore the effect of in utero PFTrDA exposure on the differentiation of fetal Leydig cells and investigate its underlying mechanisms. Pregnant Sprague-Dawley female rats were daily administered by gavage of PFTrDA at doses of 0, 1, 5, and 10 mg/kg from gestational day 14 to 21. PFTrDA had no effect on the body weight of dams, but significantly reduced the body weight and anogenital distance of male pups at birth at a dose of 10 mg/kg. PFTrDA significantly decreased serum testosterone levels as low as 1 mg/kg. PFTrDA did not affect fetal Leydig cell number, but promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg. PFTrDA down-regulated the expression of Insl3, Lhcgr, Scarb1, Star, Hsd3b1, Cyp17a1, Nr5a1, and Dhh as well as their proteins. PFTrDA lowered the levels of antioxidants (SOD1, CAT, and GPX1), induced autophagy as shown by increased levels of LC3II and beclin1, and reduced the phosphorylation of mTOR. In conclusion, PFTrDA inhibits the differentiation of fetal Leydig cells in male pups after in utero exposure mainly through increasing oxidative stress and inducing autophagy.


Assuntos
Testículo , Testosterona , Animais , Autofagia , Diferenciação Celular , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Estresse Oxidativo , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testosterona/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-33670275

RESUMO

Advancement in the field of nanotechnology has prompted the need to elucidate the deleterious effects of nanoparticles (NPs) on reproductive health. Many studies have reported on the health safety issues related to NPs by investigating their exposure routes, deposition and toxic effects on different primary and secondary organs but few studies have focused on NPs' deposition in reproductive organs. Noteworthy, even fewer studies have dealt with the toxic effects of NPs on reproductive indices and sperm parameters (such as sperm number, motility and morphology) by evaluating, for instance, the histopathology of seminiferous tubules and testosterone levels. To date, the research suggests that NPs can easily cross the blood testes barrier and, after accumulation in the testis, induce adverse effects on spermatogenesis. This review aims to summarize the available literature on the risks induced by NPs on the male reproductive system.


Assuntos
Infertilidade Masculina , Nanopartículas , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Nanopartículas/toxicidade , Estresse Oxidativo , Contagem de Espermatozoides , Motilidade Espermática , Espermatogênese , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
17.
Toxicology ; 455: 152761, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33766575

RESUMO

Several studies have reported the effects of atrazine on the gonads of many experimental models. However, the short-term effects of in vivo exposure to atrazine on the testes of mice are not well clarified. Here we reported that adult BalB/c mice exposed to atrazine (50 mg kg-1 body weight) by gavage for three consecutive days have reduced numbers of 3ß-hydroxysteroid dehydrogenase positive Leydig cells (LCs), associated with increased in situ cell death fluorescence and caspase-3 immuno-expression in the testes. Consequently, immunostaining for cell cycle gene regulators showed increased expressions of p45, accompanied with increased expressions of cyclin D2 and E2. Histological observations of the gonads showed reduced number of germ cells in particular areas, sloughed seminiferous epithelium, presence of giant apoptotic cells close to the seminiferous tubule lumen and in the epididymal lumen along with low numbers of Leydig cells in the testicular interstitial areas. Similarly, LCs isolated from the testes of BalB/c mice that were exposed to atrazine (0.5, 25, 50 mg kg-1 body weight) in the same manner as in the first experiment presented dose-dependent increased caspase-3 activity, decreased cell viability, intratesticular and serum testosterone concentrations and LCs testosterone secretion. In summary, atrazine appears to directly decrease the number of testosterone secreting LCs in mice through apoptosis.


Assuntos
Atrazina/toxicidade , Herbicidas/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Testosterona/metabolismo , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Atrazina/administração & dosagem , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Herbicidas/administração & dosagem , Células Intersticiais do Testículo/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Anim Sci J ; 92(1): e13520, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33522052

RESUMO

The current study evaluates the effects of early (8th week) and late (16th week of age) weaning of male goat kids on their body growth, testicular growth, sexual behavior, plasma testosterone concentration, and pubertal age. Early (n = 6) and late (n = 7) weaned Beetal bucks were weekly monitored from 18th to 38th week for their body weight, scrotal circumference, testicular volume, testicular echogenicity (via ultrasonography), sexual activities, and plasma testosterone concentration. In comparison to early-weaned, late-weaned bucks showed a marked increase (p < .05) in body weight (11.4 ± 0.8 vs. 13.7 ± 0.6kg), testicular volume (44.1 ± 7.2 vs. 79.8 ± 18.7cm3 ), scrotal circumference (10.7 ± 0.6 vs. 12.8 ± 0.7cm), and testicular echogenicity (28.3 ± 2.7 vs. 38.3 ± 2.1) from 18th, 28th, 21st, and 24th week onward, respectively. Sexual activities started earlier in late- than early-weaned bucks (22nd vs. 25th week, respectively). Moreover, the sexual behavior index was better (p < .05) after the 34th week in late than early-weaned bucks. The plasma concentration of testosterone (at 39 weeks of age) was relatively more and the onset of puberty was 2-3 weeks earlier (p < .05) in late than early-weaned bucks. In conclusion, age-based early weaning of male kids impairs their testicular growth, sexual behavior, and age at puberty compared to conventional weaning.


Assuntos
Peso Corporal , Cabras/metabolismo , Cabras/fisiologia , Puberdade/fisiologia , Comportamento Sexual Animal/fisiologia , Testículo/crescimento & desenvolvimento , Testosterona/metabolismo , Desmame , Fatores Etários , Animais , Cabras/crescimento & desenvolvimento , Masculino , Testosterona/sangue
20.
Life Sci ; 271: 119179, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577849

RESUMO

BACKGROUND: Male infertility and reproductive dysfunctions have become major global health problems. Although several causative factors have been attributed to this challenge, of importance are alterations in maternal-foetal environment, diet-induced transcriptional changes and dysregulation in chemical signaling via hypothalamic-gonadal axis. AIM: The present study investigated the impact of maternal high-fat diet (HFD) consumption and the putative role of Quercetin-3-O-rutinoside on reproductive functions of male offspring rats at critical developmental stages with a quest to unravel the underpinned molecular changes. MATERIALS AND METHODS: Fifty-six pregnant rats (previously fed normal diet ND) or 45% HFD) were maintained on supplemented chow (150 mg/kg QR) - ND/QR, HFD/QR throughout gestation. Subsequently, dams (n = 7) and offspring (n = 6) were sacrificed at post-natal day (PND) 21, 28 and 35, respectively, and the blood, placenta, hypothalamus (HT), and testicular samples were processed for molecular analysis of Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), testosterone, chemerin, chemokine-like receptor 1 (CMKLR1), tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and nuclear factor kappa B (NF-κB). KEY FINDINGS: We observed a significant decrease in GnRH level in the HFD group at PND21 and PND28 in male offspring and treatment with QR significantly reduced GnRH. There was a significant reduction in LH levels in the HFD group at PND 21 in the male offspring accompanied by a significant decrease in testosterone level at PND 28 and PND35 which appears to be age dependent. In the HT, Chemerin and CMKLR1 was significantly upregulated in the HFD group at PND 21 and PND 35 respectively while CMKLR1 was significantly downregulated in the HFD group of the placenta and testis at PND 21. TNF-α, IL-1ß and NF-κB were also expressed in the placenta, HT and testis at PND 21. SIGNIFICANCE: Male fertility is affected by maternal HFD consumption while chemerin, CMKLR1 and TNF-α, may play a significant role in male steroidogenesis. Treatment with QR had little or no ameliorative effect on HFD induced alterations in male reproductive functions.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Glucosídeos/farmacologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Quercetina/análogos & derivados , Reprodução/fisiologia , Testículo/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/metabolismo
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