RESUMEN
Orexins (OXs) are neuropeptides which regulate various physiological processes. OXs exist in two different forms, mainly orexin A (OXA) and orexin B (OXB) and their effects are mediated via OX1R and OX2R. Presence of OXB and OX2R in mouse testis is also reported. However, the role of OXB/OX2R in the male gonad remains unexplored. Herein we investigated the role of OXB/OX2R system in testicular physiology under in vivo and ex vivo conditions. Adult mice were given a single dose of bilateral intratesticular injection of siRNA targeting OX2R and were sacrificed 96 h post-injection. OX2R-knockdown potentiated serum and intratesticular testosterone levels with up-regulation in the expressions of major steroidogenic proteins. Germ cell proliferation also increased in siRNA-treated mice. Results of the ex vivo experiment also supported the findings of the in vivo study. In conclusion, OX2R may regulate testosterone production and thereby control the fine-tuning between steroidogenesis and germ cell dynamics.
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In recent decades, there has been a substantial decline in sperm quality in humans, with lifestyle factors playing a major role in this trend. There are several lifestyle factors which are contributing to male infertility. This review, however, discusses factors such as obesity, diet/nutrition, psychological stress, radiation exposure, cigarette smoking, and alcohol use with reference to male infertility. Sperm count, motility, morphology and sperm DNA may be adversely affected by lifestyle factors, which may also affect the endocrine regulation of reproductive function. The decline in male fertility has a significant impact on fertility rates, and the resulting implications for the human population make this a serious public health concern in the twenty-first century. Thus, lifestyle interventions through a specific framework of educational, environmental, nutritional/physical exercise, and psychological support coupled with the use of nutritional antioxidants supplements can help couples achieve better health and well-being and improve their fertility prospects or increase their chances of conception.
Asunto(s)
Infertilidad Masculina , Estilo de Vida , Salud Reproductiva , Humanos , Masculino , Infertilidad Masculina/etiología , Obesidad , DietaRESUMEN
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), are employed in various manufactured products to prevent fires, slow down their spread and reduce the resulting damages. Decabromodiphenyl ether (BDE-209), an example of PBDEs, accounts for approximately 82 % of the total production of PBDEs. BDE-209 is a thyroid hormone (TH)-disrupting chemical owing to its structural similarity with TH. Currently, increase in the level of BDE-209 in biological samples has become a major issue because of its widespread use. BDE-209 causes male reproductive toxicity mainly via impairment of steroidogenesis, generation of oxidative stress (OS) and interference with germ cell dynamics. Further, exposure to this chemical can affect metabolic status, sperm concentration, epigenetic regulation of various developmental genes and integrity of blood-testis barrier in murine testis. However, the possible adverse effects of BDE-209 and its mechanism of action on the male reproductive health have not yet been critically evaluated. Hence, the present review article, with the help of available literature, aims to elucidate the reproductive toxicity of BDE-209 in relation to thyroid dysfunction in rodents. Further, several crucial pathways have been also highlighted in order to strengthen our knowledge on BDE-209-induced male reproductive toxicity. Data were extracted from scientific articles available in PubMed, Web of Science, and other databases. A thorough understanding of the risk assessment of BDE-209 exposure and mechanisms of its action is crucial for greater awareness of the potential threat of this BFR to preserve male fertility.
RESUMEN
The orexins (OXs) were first reported in hypothalamus of rat, and they play an important role in diverse physiological actions. The OXs consist of orexin A (OXA) and orexin B (OXB) peptides and their actions are mediated via two G-protein-coupled receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), respectively. Presence of OXA and OX1R has been also reported in peripheral organs like reproductive tissues. These findings, therefore, highlight a possible role of OXs and their receptors in male reproductive health. Though, expression and localization of OXB and OX2R in the testis and their role in spermatogenesis are not finally clarified. Herein, we elucidated the localization and the patterns of expression of OXB and OX2R in Parkes mice testes during postnatal development. Results suggest that the precursor prepro-orexin (PPO), OXB and OX2R are expressed at the transcript and protein levels in mouse testis throughout the postnatal development. Immunostaining further showed the localization of OXB and OX2R both in interstitium and tubular compartments of the testis. On 7 day postpartum (7 dpp), only spermatogonia showed immunoreactivity of OXB and OX2R, while at 14, 28, 42 and 90 dpp, immunolocalization of OXB and OX2R were noted in the seminiferous tubules, especially in leptotene, pachytene spermatocytes, round and elongating spermatids, and in Leydig cells and Sertoli cells. The immunoreactivity of OXB and OX2R appeared to be stage-specific in adult mouse testis. The results suggest the expression of OXB and OX2R in mouse testis and their possible regulatory role in spermatogenesis and steroidogenesis.
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Espermátides , Testículo , Animales , Masculino , Ratones , Células Intersticiales del Testículo/metabolismo , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Orexinas/genética , Orexinas/metabolismo , Espermátides/metabolismo , Testículo/metabolismoRESUMEN
Several processes including oxidative stress, apoptosis, inflammation and autophagy are related to testicular function. Recent studies indicate that a crosstalk between apoptosis and autophagy is essential in regulating testicular function. Autophagy and apoptosis communicate with each other in a complex way, allowing them to work for or against each other in testicular cell survival and death. Several xenobiotics especially endocrine-disrupting chemicals (EDCs) have caused reproductive toxicity because of their potential to modify the rate of autophagy and trigger apoptosis. Therefore, the purpose of the present review was to shed light on how autophagy and apoptosis interact together in the testis.
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Disruptores Endocrinos , Espermatogénesis , Masculino , Humanos , Autofagia , Apoptosis , Testículo , Estrés OxidativoRESUMEN
Thyroid hormone (T3 ) acts on the testis via thyroid hormone receptor alpha 1 (TRα1), though the cellular localization of TRα1 in testis remains controversial. Studies on the presence of TRα1 in the epididymis are also lacking. The present study, therefore, examined the cellular localization and expression pattern of TRα1 in testis and epididymis of Parkes mice during postnatal development. Immunohistochemical results showed localization of TRα1 in interstitial and tubular compartments of the testis all through the development. On postnatal day (PND) 14, only leptotene spermatocytes showed TRα1-immunoreactivity in the testis, while at PND 28, 42, and 90, a diverse staining pattern for TRα1 was seen in almost all the seminiferous tubules mainly in leptotene spermatocytes, round and elongating spermatids, and in Leydig cells. Further, qRT-PCR and immunoblot analyses showed that TRα1 was expressed in the testis at the transcript as well as protein level throughout the postnatal development. TRα1 was also seen in principal cells of the epididymis, with maximal expression at PND 90. TRα1 was also present in cauda epididymidal spermatozoa of adult mice at PND 90. The results suggest that TRα1 is expressed in the testis and epididymis and that it may help to regulate the spermatogenic process and male fertility.
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Epidídimo , Testículo , Receptores alfa de Hormona Tiroidea/genética , Animales , Epidídimo/crecimiento & desarrollo , Epidídimo/metabolismo , Inmunohistoquímica , Masculino , Ratones , Espermátides/metabolismo , Testículo/metabolismo , Receptores alfa de Hormona Tiroidea/metabolismoRESUMEN
Fenugreek seed exhibits antidiabetic, antineoplastic, hepatoprotective, antidepressant and immunomodulatory properties. Fenugreek also causes antifertility effects in rodents. However, the impact of fenugreek seed on male reproduction and the possible mode of its action are not properly evaluated. Herein, we examined the effect of aqueous seed extract of fenugreek (FSE) and the possible mechanism of its action on male reproductive health in mice. Parkes mice were orally administered FSE (600 mg/kg body weight/day) or distilled water for 28 and 56 days, respectively. Various sperm parameters, histopathology, serum testosterone level and fertility indices were assessed. Furthermore, steroidogenic enzymes activities, oxidative status and germ cell dynamics in the testis were evaluated. Toxicological endpoints were also assessed. Treatment with FSE caused degenerative changes in the testis histoarchitecture. The treatment also affected various sperm parameters and concentrations of sialic acid and fructose in the epididymis and seminal vesicle, respectively. Fenugreek treatment also had negative impact on oxidative status and germ cell dynamics in the testis; fertility indices were also affected in female mice impregnated by the extract-treated male mice, though libido of the treated male mice remained unaffected. Results show that treatment with FSE caused adverse effects on the male reproductive health and pregnancy outcome in Parkes mice.
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Trigonella , Animales , Femenino , Masculino , Ratones , Extractos Vegetales/farmacología , Embarazo , Semillas , Espermatogénesis , TestículoRESUMEN
QRFP, an orexigenic neuropeptide, binds to its cognate receptor GPR103 and regulates various biological functions. We have recently shown that QRFP and its receptor are present in mice testes and that their expression is high during early postnatal period. The present study aimed to investigate the effect of sustained high level of QRFP on Sertoli cells proliferation and differentiation and to relate these events with germ cell differentiation and lumen formation in the seminiferous tubules in mice testes during prepubertal period. QRFP was injected intraperitoneally to male mice from postnatal day 5 to 16. Morphometric analysis and various markers related to Sertoli cell maturation (WT1, p27kip1, AMH, AR and CYP19A1) and germ cell proliferation and differentiation (PCNA, GDNF and c-Kit) were evaluated. QRFP administration caused an early lumen formation in the seminiferous tubules in testis of treated mice. Further, there was a significant increase in p27kip1 expression and a marked decrease in AMH expression in QRFP-treated mice compared to controls. However, no appreciable change was noted in AR expression in treated mice. QRFP treatment also caused an increase in c-Kit expression in treated mice compared to controls, suggesting an accelerated spermatogonial differentiation in testis of QRFP-treated mice. Taken together, the present results suggest that the prolonged high level of QRFP increases Sertoli cell maturation, which, in turn, plays a contributory role in increasing the pace of germ cell differentiation and formation of lumen in the seminiferous tubules.
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Neuropéptidos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células de Sertoli/metabolismo , Testículo/metabolismo , Animales , Proliferación Celular/fisiología , Masculino , Ratones , Células de Sertoli/citología , Espermatogonias/citología , Espermatogonias/metabolismo , Testículo/citología , Testículo/crecimiento & desarrolloRESUMEN
Environmental conditions such as temperature, light and food availability are known to influence the physiological status of animals. The male dromedary camel (Camelus dromedarius) is considered as a seasonal breeder with maximal sexual activity during certain period of the year followed by a decrease in activity during the remaining period. On the other hand, the male camel is also shown as an atypical seasonal breeder because this does not undergo sexual quiescence with complete cessation of spermatogenesis. This animal, however, shows remarkable physiological and behavioral changes during its maximal sexual activity. The annual breeding (rutting) period also influences the epididymis. In this review, an attempt has been made to present the available literature pertaining to gross anatomical, histological, histochemical, immunohistochemical and molecular changes in camel epididymis during breeding and nonbreeding periods, and the changes are believed to be correlated with male sexual behavior and libido. This review may also exhibit the dromedary camel breeding period, which is still unresolved, and thus may prove helpful in determining the exact time of mating, which is important for the success of assisted reproductive outcomes. Further, the review may contribute to a better understanding of the epididymal physiology in camel and may also prove useful in improving reproductive efficiency and population of this animal.
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Camelus , Epidídimo , Reproducción/fisiología , Animales , Cruzamiento , Camelus/anatomía & histología , Camelus/fisiología , Epidídimo/anatomía & histología , Epidídimo/metabolismo , Masculino , Conducta Sexual Animal , Espermatogénesis/fisiología , TemperaturaRESUMEN
Decabromodiphenyl ether (BDE-209) is widely used as a flame retardant in many products like electronic equipments, plastics, furniture and textiles. BDE-209, a thyroid hormones (THs)-disrupting chemical, affects male reproductive health through altered THs status in mouse model. The present study was designed in continuation to our earlier work to elucidate whether early life exposure to BDE-209 has a long term potential risk to male reproductive health. This study, therefore, aimed to evaluate the effect of maternal BDE-209 exposure during lactation and to elucidate possible mechanism(s) of its action on male reproduction in adult Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive controls and vehicle-treated controls. Male pups of lactating dams were euthanized at PND 75. Maternal BDE-209 exposure during lactation markedly affected histoarchitecture of testis and testosterone production with concomitant down-regulation in the expression of various steroidogenic markers in adult offspring. Maternal exposure to BDE-209 during lactation also interfered with germ cell dynamics and oxidative status in testes of adult mice offspring. A decreased expression of connexin 43 and androgen receptor was also evident in testes of these mice offspring; further, number, motility and viability of spermatozoa were also adversely affected in these mice. The results thus provide evidences that maternal exposure to BDE-209 during lactation causes reproductive toxicity in adult mice offspring.
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Retardadores de Llama/toxicidad , Éteres Difenilos Halogenados/toxicidad , Espermatogénesis/efectos de los fármacos , Animales , Conexina 43/metabolismo , Femenino , Células Germinativas/efectos de los fármacos , Lactancia/efectos de los fármacos , Masculino , Exposición Materna , Ratones , Receptores Androgénicos/metabolismo , Espermatozoides/efectos de los fármacos , Esteroides/metabolismo , Testículo/efectos de los fármacos , Testosterona/metabolismo , Hormonas Tiroideas/metabolismoRESUMEN
QRFP is a neuropeptide that regulates glucose homeostasis and increases insulin sensitivity in tissues. We have previously shown that QRFP and its receptor (GPR103) are predominantly expressed in germ cells and Sertoli cells, respectively, in mice testes. In the present study, we report that QRFP caused an increase in PCNA and a decrease in p27Kip1 expressions in the testis under both in vivo and ex vivo conditions. Besides, via an in vivo study, cell cycle analysis by FACS showed an increase in 2C cells and a decrease in 1C cells. QRFP also induced expression of GDNF and phosphorylation of Akt and ERK-1/2. Together these results suggest that QRFP has a proliferative effect on germ cells in mice testes, since it caused a proportional increase in the mitotic activity and the number of spermatogonial cells. Further, observations of increased expressions of STAT-3 and Neurog3 in treated mice suggest that QRFP treatment regulates priming of undifferentiated spermatogonia to undergo differentiation, while a decrease in c-Kit expression indicate that spermatogonia at this time point are in an undifferentiated state. In addition, QRFP administration also caused an increase in intratesticular levels of glucose and lactate, and in LDH activity accompanied by increased expressions of GLUT-3 and LDH-C in the testis. Also, the phosphorylation of IR-ß and expressions of p-Akt and p-mTOR were increased under ex vivo conditions in testicular tissue. In conclusion, our findings suggest that QRFP treatment caused proliferation of germ cells independently from the hypothalamic-pituitary axis via regulation of testicular energy metabolism.
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Diferenciación Celular , Proliferación Celular , Metabolismo Energético , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas , Espermatogonias/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Línea Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/farmacología , Masculino , Ratones , Proteínas del Tejido Nervioso/metabolismo , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Factor de Transcripción STAT3/metabolismo , Espermatogonias/citologíaRESUMEN
This review attempts to collate existing data and provide the perspectives for future studies on the effects of plants on the male gonads. For many of these medicinal plants such as Lepidium meyenii, Rupus coreanus, Tribulus terrestres, Panax ginseng, Petasites japonicas, Apium graveolens, Eurycoma longifólia, Pedalium murex, Corchorus depressus, Mucuna pruriens, Astragalus membranaceus, Nigella sativa, Crataegus monogyna, Fagara tessmannii, Phaleria macrocarpa, Anacyclus pyrethrum, Cynomorium songaricum and Morinda officinalis, the mechanism of actions of their active principles and crude extracts has been shown in both laboratory animals, in vitro, and human studies, and includes their antioxidant, anti-inflammatory, spermatogenesis-inducing, aphrodisiac, smooth muscle relaxing and androgenic properties. Several active chemical leads including glucosinolates, anthocyanins, protodioscin, ginsenosides, sesquiterpenes, phyto-oestrogens, quassinoids, diosgenin, thymoquinone, proanthocyanidins and bajijiasu isolated from these plants are known to have target effects on the testis, but efforts have been limited in their application at the clinical level. There still appear to be many more extracts of medicinal plants that have not been characterised to determine the phytochemicals unique to them that have target effects on the gonads. Further, collaborative efforts at isolating pro-drug candidates from medicinal plants for studies at the molecular, cellular and clinical level towards elucidating their mechanisms of action on the testes are therefore warranted in the light of the current male fertility crisis.
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Descubrimiento de Drogas , Infertilidad Masculina/tratamiento farmacológico , Medicina Tradicional/métodos , Extractos Vegetales/farmacología , Plantas Medicinales/química , Animales , Humanos , Masculino , Modelos Animales , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacosRESUMEN
Perfluoroalkyl acids (PFAAs) are anthropogenic compounds used globally in a variety of commercial products. Perfluorononanoic acid (PFNA), a member of PFAAs, is detected in human blood and this has been reported to cause hepatotoxic, immunotoxic, and developmental and testicular toxic effects in laboratory animals. We have recently shown that the acute exposure to PFNA in prepubertal Parkes (P) mice impairs spermatogenesis by inducing oxidative stress and inhibiting testosterone biosynthesis in the testis. The present study was aimed to examine the effect of acute exposure to PFNA in prepubertal P mice on germ cell dynamics and to understand the possible mechanisms of action of this compound on testicular functions. PFNA (2 and 5â¯mg/kg body weight) was orally administered to male mice for 14 days from postnatal day 25-38. The treatment caused a decrease in overall germ cell transformation. The results also reveal that impairment in testicular functions in treated mice is associated with alterations in cholesterol and glucose homeostasis; further, an inhibition in expressions of growth hormone receptor (GHR), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-1 receptor (IGF-1R), androgen receptor (AR), phosphorylated mammalian target of rapamycin (p-mTOR) and peroxisome proliferator activated receptor α (PPAR α) in the testis is also implicated in this action. The findings thus suggest involvement of multiple factors which altogether contribute to the alterations in spermatogenic process and testosterone production following acute exposure to PFNA in prepubertal mice.
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Fluorocarburos/toxicidad , Células Germinativas/efectos de los fármacos , Homeostasis/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Glucemia/metabolismo , Colesterol/sangre , Ácidos Grasos , Fluorocarburos/administración & dosificación , Células Germinativas/metabolismo , Células Germinativas/patología , Masculino , Ratones , Testículo/metabolismo , Pruebas de Toxicidad AgudaRESUMEN
Perfluoroalkyl acids (PFAAs) are widely used in commercial products and are found in many goods of daily use. Perfluorononanoic acid (PFNA) is one of the PFAAs that possesses endocrine disrupting properties and we have recently shown that PFNA affects testicular functions in Parkes mice. Exposure to environmental endocrine disruptors during fetal life is believed to affect gonadal development and they might produce reproductive abnormalities in males. Therefore, the present study examined the effect of gestational exposure to PFNA on the testes of neonatal mice offspring. Pregnant Parkes mice were orally administered PFNA (2 and 5 mg/kg body weight) or distilled water from gestational day 12 until parturition. Male pups were killed on postnatal day 3. PFNA treatment decreased testosterone biosynthesis by inhibiting expression of steroidogenic acute regulatory protein, cytochrome P450scc, and 3ß- and 17ß-hydroxysteroid dehydrogenase; proliferation of testicular cells was also affected in treated mice. Furthermore, a marked decrease in expression of Wilms tumor 1, steroidogenic factor 1 and insulin-like factor 3 was noted in neonatal mice testes, indicating that the PFNA treatment may affect the development of the testis. Moreover, observation of the dose-related expression of anti-müllerian hormone and c-Kit in neonatal mice testes is also suggestive of an interference with gonadal development by PFNA exposure. In conclusion, the results suggest that the gestational exposure to PFNA decreased testosterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health.
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Disruptores Endocrinos/toxicidad , Fluorocarburos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Animales Recién Nacidos , Desarrollo Embrionario/efectos de los fármacos , Ácidos Grasos , Femenino , Masculino , Ratones , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Testículo/patología , Testosterona/metabolismoRESUMEN
Decabromodiphenyl ether (BDE-209), a flame retardant, interferes with thyroid homeostasis and androgen biosynthesis. BDE-209 evokes hyperglycemia through impaired glucose homeostasis in rat liver. This study is in continuation to our earlier work for a better understanding of whether or not BDE-209 affects testicular and epididymal physiology in relation to oxidative status in peripupertal mice offspring. Lactating female Parkes mice were orally gavaged with 500 and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28. Male pups of lactating dams were sacrificed at PND 42. Maternal BDE-209 exposure during lactation increased apoptosis and oxidative status with altered expressions of various cell survival (Bcl-2), apoptotic (Bax and caspase-3) and oxidative stress (Nrf2 and HO-1) markers in testes and epididymis of peripubertal mice offspring. Testicular glucose and lactate concentrations were markedly reduced in these pups with down-regulation in GLUT3 and GLUT8 expressions and decreased LDH activity. Maternal BDE-209 exposure markedly affected fertility potential, epididymal histology, sialic acid concentration and sperm quality with decreased expression of epididymal Cx43 and AR in these mice offspring. Results thus suggest that maternal BDE-209 exposure during lactation causes reproductive toxicity in peripubertal mice offspring.
Asunto(s)
Epidídimo/efectos de los fármacos , Fertilidad/efectos de los fármacos , Éteres Difenilos Halogenados/toxicidad , Infertilidad Masculina/inducido químicamente , Lactancia , Estrés Oxidativo/efectos de los fármacos , Testículo/efectos de los fármacos , Factores de Edad , Animales , Conexina 43/metabolismo , Epidídimo/metabolismo , Epidídimo/patología , Femenino , Glucosa/metabolismo , Hemo-Oxigenasa 1/metabolismo , Homeostasis , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Infertilidad Masculina/fisiopatología , Masculino , Exposición Materna , Proteínas de la Membrana/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Embarazo , Receptores Androgénicos/metabolismo , Desarrollo Sexual , Transducción de Señal/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Espermatozoides/patología , Testículo/metabolismo , Testículo/patologíaRESUMEN
Long term exposure of electromagnetic radiations (EMR) from cell phones and Wi-Fi hold greater propensity to cause anxiety disorders. However, the studies investigating the effects of repeated exposure of EMR are limited. Therefore, we investigated the effects of repeated exposure of discrete frequencies of EMR in experimental animals. Male rats were exposed to EMR (900, 1800 and 2450â¯MHz) for 28 (1â¯h/day) days. Long term exposure of EMR (2450â¯MHz) induced anxiety like behavior. It deregulated the hypothalamic pituitary adrenal (HPA) axis in rats as observed by increase in plasma corticosterone levels apart from decreased corticotrophin releasing hormone-2 (CRH-2) and Glucocorticoid receptor (GR) expression in amygdala. Further, it impaired mitochondrial function and integrity. The expression of Bcl2 showed significant decrease while Bax and ratio of Bax: Bcl2 were increased in the mitochondria and vice versa in cytoplasm indicating altered regulation of apoptosis. EMR exposure caused release of cytochrome-c and expression of caspase-9 ensuing activation of apoptotic cell death. Additional set of experiments performed to estimate the pattern of cell death showed necrotic and apoptotic amygdalar cell death after EMR exposure. Histopathological studies also revealed a significant decrease in neuronal cells in amygdala. The above findings indicate that long-term exposure of EMR radiation (2450â¯MHz) acts as a stressor and induces anxiety-like behaviors with concomitant pathophysiological changes in EMR subjected rats.
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Ansiedad/metabolismo , Ansiedad/patología , Radiación Electromagnética , Estrés Psicológico/metabolismo , Estrés Psicológico/patología , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/efectos de la radiación , Animales , Ansiedad/etiología , Muerte Celular/fisiología , Muerte Celular/efectos de la radiación , Corticosterona/sangre , Masculino , Aprendizaje por Laberinto/fisiología , Aprendizaje por Laberinto/efectos de la radiación , Ratas , Estrés Psicológico/etiología , Factores de TiempoRESUMEN
Pyroglutamylated RFamide peptide (QRFP), a neuropeptide, binds to its receptor GPR103 and influences various biological functions. In the present study, expression and localization of QRFP and GPR103 in mouse testis during post-natal development were investigated. The results showed that QRFP and GPR103 and also the isoforms of the receptor, viz. GPR103A and GPR103B were expressed in mouse testis during post-natal development. Expression of QRFP and its receptor was high during the early periods of post-natal development. Immunohistochemical study demonstrated the localization of QRFP and GPR103 in both interstitial and tubular compartments of the testis throughout post-natal development. A shift in the germ cell types expressing QRFP and its receptor along the course of testicular development and also a prominent immunoreactivity of QRFP in germ cells and of GPR103 in Sertoli cells was observed. Further, the immunoreactivity of QRFP and GPR103 appeared to be stage-specific in spermatogenetically active testis. Besides in intercellular spaces, localization of QRFP was also noticed in nuclei of germ cells. In conclusion, the present results suggest potential involvement of QRFP system in the development, proliferation and differentiation of testicular cells, possibly by regulating the energy requirement for these processes.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Péptidos/metabolismo , Receptores Acoplados a Proteínas G/genética , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Transporte Activo de Núcleo Celular , Animales , Núcleo Celular/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Masculino , Ratones , Testículo/citologíaRESUMEN
Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that they are ubiquitous and persistent in the environment. Perfluorononanoic acid (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous acute exposure studies have shown the adverse effect of PFNA on the testis. The present study was aimed to examine the effect of chronic PFNA exposure, from prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male mice and to investigate the possible mechanism(s) of its action. PFNA (0.2 and 0.5 mg/kg) was orally administered to P male mice for 90 days from prepuberty (postnatal day [PND] 25) to adulthood (PND 114). Histologically, testes in PFNA-treated mice showed non-uniform degenerative changes in the seminiferous tubules. The treatment also had adverse effects on testicular expression of steroidogenic markers, serum levels of cholesterol and testosterone, sperm parameters and on litter size. A marked increase in the level of lipid peroxidation and decrease in the activities of antioxidant enzymes were observed in the testis of PFNA-treated mice compared to controls. Further, a significant decrease in expression of proliferating cell nuclear antigen (PCNA) and in the number of PCNA-positive cells, and an increase in expression of caspase-3 were also noted in PFNA-treated mice testis. In conclusion, the results suggest that chronic exposure to PFNA in male mice interferes with testosterone biosynthesis and causes oxidative stress in the testis, leading to alterations in spermatogenesis, sperm quality and fertility potential.
Asunto(s)
Fertilidad/efectos de los fármacos , Fluorocarburos/toxicidad , Espermatogénesis/efectos de los fármacos , Testosterona/biosíntesis , Animales , Ácidos Grasos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Estrés Oxidativo , Antígeno Nuclear de Célula en Proliferación/análisis , Túbulos Seminíferos/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patologíaRESUMEN
Perfluoroalkyl acids (PFAAs) are widely used in industrial and commercial products and possess endocrine disrupting properties. Perfluorononanoic acid (PFNA), one of PFAAs, has been mainly reported to produce testicular toxicity in adult animals. The objective of the present study was to examine the effect of acute exposure of PFNA to prepubertal male Parkes (P) mice on spermatogenesis and testicular steroidogenesis, and to study the possible mechanism(s) of its action. PFNA (2 and 5â¯mg/kg) was orally administered to male P mice for 14 days from postnatal day 25-38. Histologically, testis in PFNA-treated mice showed non-uniform diverse degenerative changes in the seminiferous tubules; both normal and affected tubules were seen in the same testicular sections. The treatment caused a reduction in intra-testicular and serum testosterone levels accompanied by a decrease in testicular expression of SF1, StAR, CYP11A1, and 3ß- and17ß-HSD. Further, the activity of antioxidant enzymes and expression of Nrf2 and HO-1 in the testis were markedly decreased, while the level of lipid peroxidation and expression of IKKß, NF-κB and caspase-3 were significantly increased in testis of PFNA-treated mice. There was also a decrease in PCNA expression and in PCNA-index and an increase in TUNEL-positive germ cells in testes of PFNA-treated mice. In conclusion, the results suggest that PFNA exposure to prepubertal male mice altered antioxidant enzymes activity and Nrf2-HO-1 signaling, leading to oxidative stress and a decrease in testosterone biosynthesis in the testis; these changes, in turn, caused increased apoptosis and decreased proliferation of germ cells, thereby suppression of spermatogenesis.
Asunto(s)
Disruptores Endocrinos/toxicidad , Fluorocarburos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testosterona/biosíntesis , Envejecimiento/metabolismo , Animales , Antioxidantes/metabolismo , Ácidos Grasos , Masculino , Ratones , Transducción de Señal , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Testículo/patología , Testosterona/sangreRESUMEN
Decabromodiphenyl ether (BDE-209), a congener of polybrominated diphenyl ethers (PBDEs), is used as flame retardant and affects thyroid homeostasis. Thyroid hormones (THs) play crucial role in Leydig cell differentiation and steroidogenesis during early life. Present study examined the effect of maternal BDE-209 exposure during lactation on testicular steroidogenesis and spermatogenesis in relation to thyroid hormone receptor alpha 1 (THRα1) and possible mechanism(s) of its action in prepubertal Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700â¯mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28. Lactating mothers and male pups were sacrificed on PND 28. Maternal BDE-209 exposure markedly affected testicular histopathology, steroidogenesis and germ cell dynamics with downregulated expressions of various steroidogenic markers in mice offspring. Serum THs levels were markedly reduced in both pups and lactating mothers compared to controls. Expression of proliferating cell nuclear antigen and THRα1 also deceased in testes of BDE-209-exposed mice offspring. In silico analysis by molecular docking was performed successfully for steroidogenic facor-1 (SF-1) and THRα1 with BDE-209 and T3. Maternal BDE-209 exposure during lactation affects testicular steroidogenesis, spermatogenesis and expression of THRα1 in prepubertal mice offspring through downregulation of SF-1.