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INTRODUCTION: The sensory innervation of the hand is getting a lot of attention because of the quick surge in the usage of local anesthesia and the progress of plastic surgeries. It is significant to know the likely disparities in the sensory innervation of the hand to prevent mistakes while analyzing the symptoms or misdiagnosing the nerve pathology. So this study aims to assess the sensory innervation of the hand. MATERIALS AND METHOD: The study was carried out on 54 upper limbs. All the branches of the median, ulnar and radial nerve were traced. Variations in the distribution and anastomoses were noted. RESULTS: Anastomosis between the median and ulnar nerve was found in 12.95% of cases. In all cadavers, 3 1/2 digits are supplied by the median nerve and 1 1/2 digits by the ulnar nerve bilaterally in the palms. In all cadavers 2 1/2 digits, each is supplied by radial and ulnar nerve bilaterally on the dorsum of hands. CONCLUSION: These anatomic conclusions will aid hand surgeons in identifying differences in sensory losses after either dorsal or palmar injuries.
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Mãos , Extremidade Superior , Humanos , Anastomose Cirúrgica , Cadáver , ÍndiaRESUMO
PURPOSE: Anatomical knowledge of the hypoglossal canal is very important in relation to drilling of occipital condyle, jugular tubercle etc. So, this study was conducted to identify various morphometric and morphological features of the hypoglossal canal and its distance from adjacent structures relative to stable and reliable anatomic landmarks. METHODS: The study was performed on 142 hypoglossal canals of 71 adult human dry skulls. The parameters measured were the transverse, vertical diameter, depth of the hypoglossal canal. The distances from the hypoglossal canal to the foramen magnum, occipital condyle and jugular foramen were also noted. In addition, the different locations of the hypoglossal canal orifices in relation to the occipital condyle were assessed. The different shapes and types of the hypoglossal canal were also noted. RESULTS: There was significant difference (p < 0.05) in measurements taken on the right and left sides in males and females. The intracranial orifice of hypoglossal canal was present in middle 1/3rd in 100% of occipital condyle for both genders. The extracranial orifice of the hypoglossal canal was found to be in the anterior 1/3rd in 99% and 93.7% for male and female, respectively. Simple hypoglossal canal with no traces of partition was found to be more in males and females. The most common shape noted was oval both in males and females (71.8% and 68.7% respectively). CONCLUSION: The results of the dimensions of the hypoglossal canal and its distance from other bony landmarks will be helpful for neurosurgeons to plan which surgical approaches should be undertaken while doing various surgeries in posterior cranial fossa.
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Osso Occipital , Procedimentos Ortopédicos , Adulto , Feminino , Masculino , Humanos , Osso Occipital/cirurgia , Osso Occipital/anatomia & histologia , Forame Magno/cirurgia , Forame Magno/anatomia & histologia , Crânio , Procedimentos Neurocirúrgicos/métodos , Fossa Craniana Posterior/cirurgia , Fossa Craniana Posterior/anatomia & histologia , Base do Crânio/cirurgia , Base do Crânio/anatomia & histologiaRESUMO
CONTEXT: Tuberculosis is one of the major infectious diseases, with people of reproductive age group having a high risk of infection. AIMS: The present study was designed to understand the consequences of anti-tuberculosis drugs (ATDs) used in DOTS (directly observed treatment short course) schedule on ovarian function. METHODS: Adult female Swiss albino mice were orally administered with combinations of ATDs used in the DOTS schedule every day for 4weeks. At 2weeks after the cessation of ATDs administration, the endocrine changes and ovarian function were assessed in mice. KEY RESULTS: Administration of ATDs to mice resulted in a prolonged estrous cycle, reduced ovarian follicle reserve, alteration in FSH, LH, and progesterone level, and decreased the number of ovulated oocytes. Further, the degree of fragmentation, degeneration, abnormal distribution of cytoplasmic organelles, abnormal spindle organisation, and chromosomal misalignment were higher in oocytes that were ovulated following superovulation. Blastocysts derived from ATDs treated mice had significantly lower total cell numbers and greater DNA damage. A marginal increase in the number of resorbed fetuses was observed in all the ATDs treated groups except in the multidrug resistance treatment group. Male progeny of ATDs treated mice had decreased sperm count and lower progressive motility, while female progeny exhibited a non-significant reduction in the number of oocytes ovulated. CONCLUSIONS: Theresults of this study suggest that ATDs can have significant adverse effects on the ovarian reserve, cytoplasmic organisation of oocytes, and can potentially cause transgenerational changes. IMPLICATIONS: The findings of the present study indicate ovarian toxicity of ATDs and warrant further research in the direction of identifying alternate drugs with minimal toxicity, and strategies to mitigate the ovarian toxicity induced by these drugs.
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Reserva Ovariana , Masculino , Camundongos , Feminino , Animais , Antituberculosos/farmacologia , Sêmen , Oócitos , SuperovulaçãoRESUMO
The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.
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Antineoplásicos Alquilantes/toxicidade , Antioxidantes/farmacologia , Curcumina/farmacologia , Ciclofosfamida/toxicidade , Nanopartículas , Espermatogônias/efeitos dos fármacos , Doenças Testiculares/prevenção & controle , Testículo/efeitos dos fármacos , Animais , Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Dano ao DNA/efeitos dos fármacos , Composição de Medicamentos , Regulação da Expressão Gênica , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/prevenção & controle , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espermatogônias/metabolismo , Espermatogônias/patologia , Doenças Testiculares/induzido quimicamente , Doenças Testiculares/metabolismo , Doenças Testiculares/patologia , Testículo/metabolismo , Testículo/patologia , Fatores de TempoRESUMO
Quinalphos (QP) is one of the most commonly used organophosphate pesticide for agriculture. In this study, adult Swiss albino male mice were orally administered with 0.25, 0.5 and 1.0 mg/kg of QP (Ekalux 25 E.C.) for ten consecutive days and the reproductive function was assessed at 35 and 70 days after QP treatment. At highest dose (1.0 mg/kg), QP exposure resulted in significant decrease in motility and increase in sperm head defects and DNA damage. Pharmacokinetic data showed a threefold increase in concentration of QP in the testis as compared to serum. QP was detectable in testes even after 24 hr of administration indicating slow clearance from tissue. In addition, high oestradiol, low testosterone level with a parallel increase in aromatase and cytochrome P450 transcript levels was observed. Significant decrease in fertilisation, lower blastocyst rate and poor blastocyst quality was observed when spermatozoa collected from QP exposed mice were subjected to in vitro fertilisation. In conclusion, exposure of QP to male mice decreases the sperm functional competence and fertilising ability, which appears to be mediated through elevated oxidative stress and altered steroidogenesis in testes.
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Compostos Organofosforados , Praguicidas , Animais , Fertilização , Masculino , Camundongos , Compostos Organotiofosforados , Praguicidas/toxicidade , Motilidade dos Espermatozoides , Espermatozoides , TestículoRESUMO
The present study was designed to investigate the effect of diet-induced obesity on endoplasmic reticulum (ER) stress in oocytes. Swiss albino mice (3 weeks old) were fed with a high-fat diet (HFD) for 8 weeks. Oocytes were assessed for lipid droplet accumulation, oxidative stress, ER stress and their developmental potential invitro. High lipid accumulation (P<0.01) and elevated intracellular levels of reactive oxygen species were observed in both germinal vesicle and MII oocytes of HFD-fed mice (P<0.05 and P<0.01 respectively compared with control). Further, expression of the ER stress markers X-box binding protein 1 (XBP1), glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4) and activating transcription factor 6 (ATF6) was significantly (P<0.001) higher in oocytes of the HFD than control group. Oocytes from HFD-fed mice exhibited poor fertilisation and blastocyst rates, a decrease in total cell number and high levels of DNA damage (P<0.01) compared with controls. In conclusion, diet-induced obesity resulted in elevated lipid levels and higher oxidative and ER stress in oocytes, which contributed to the compromised developmental potential of embryos.
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Desenvolvimento Embrionário/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Metabolismo dos Lipídeos/fisiologia , Oócitos/metabolismo , Estresse Oxidativo/fisiologia , Fator 4 Ativador da Transcrição/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Dano ao DNA , Dieta Hiperlipídica , Chaperona BiP do Retículo Endoplasmático , Feminino , Proteínas de Choque Térmico/metabolismo , Camundongos , Obesidade/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
PURPOSE: Metformin is the most commonly prescribed drug in the management of metabolic disorders such as polycystic ovarian syndrome (PCOS) and gestational diabetes in women of reproductive age. Insulin-sensitizing effect of metformin helps in improving from PCOS features such as hyperandrogenism, anovulation, and infertility. However, its ability to cross placental barrier raises concern about safety of the drug on early embryonic development. In this study, we evaluated the effect of metformin on the ovarian function and embryo development. METHODS: Adult Swiss albino female mice were administered with metformin (0, 50, 100, and 200 mg/kg body weight) for 4 weeks and assessed for reproductive function and preimplantation embryo development. Further, effect of metformin (0, 10, 25, 50, 100, 250, and 500 µg/mL) exposure to 2-cell-stage embryos was tested under in vitro conditions. RESULTS: Metformin did not alter the body weight, blood glucose, ovarian weight, and follicular reserve. However, the early embryo development was significantly affected in mice treated with metformin in vivo at highest dose. Moreover, embryos which were exposed to metformin in vitro showed dose-dependent decline in blastocyst rate and hatching rate. Furthermore, at highest concentration of metformin (500 µg/mL), all the embryos were arrested at compaction stage. CONCLUSION: The study revealed that metformin affects the early embryonic development and raises concern about its use during conception.
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Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Animais , Blastocisto/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Diabetes Gestacional/sangue , Diabetes Gestacional/fisiopatologia , Modelos Animais de Doenças , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilização in vitro/tendências , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/metabolismo , Resistência à Insulina/genética , Metformina/efeitos adversos , Camundongos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , GravidezRESUMO
The aim of the present study was to determine the effects of repeated superovulation on oocyte quality and embryo developmental potential. Female Swiss albino mice were injected with 5IU pregnant mare's serum gonadotropin followed 48h by 10IU human chorionic gonadotropin. Mice were superovulated up to four times with a gap of 7 days between each superovulation cycle. Ovarian weight increased significantly with an increasing number of superovulation cycles. Although the first stimulation cycle resulted in a threefold increase in the number of oocytes, the number of oocytes decreased gradually after subsequent stimulations. Increased cytoplasmic fragmentation, abnormal mitochondrial distribution, aggregation of Golgi apparatus, spindle damage, increased intracellular oxidative stress and a decrease in expression of octamer-binding transcription factor 4 (Oct4) expression were observed in these oocytes. Further, embryos derived from mice subjected to multiple stimulation cycles exhibited a low blastocyst rate, decreased hatching rate and increased apoptosis in blastocysts. In conclusion, the present study demonstrates that repeated superovulation adversely affects mouse oocyte quality by altering the distribution of cytoplasmic organelles, increasing oxidative stress and decreasing Oct4 expression, resulting in poor developmental potential of the embryos.
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Gonadotropinas Equinas/administração & dosagem , Fator 3 de Transcrição de Octâmero/metabolismo , Oócitos/citologia , Estresse Oxidativo , Superovulação , Animais , Blastocisto , Feminino , Cavalos , Humanos , Camundongos , Organelas , Gravidez , Fuso AcromáticoRESUMO
Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome.
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Núcleo Celular/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Inseticidas/farmacologia , Metil Paration/farmacologia , Oócitos/efeitos dos fármacos , Tamanho do Órgão , Animais , Blastocisto/efeitos dos fármacos , Contagem de Células , Feminino , Feto/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Glutationa/metabolismo , Marcação In Situ das Extremidades Cortadas , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Oócitos/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Placenta/efeitos dos fármacos , Gravidez , Reprodução/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacosRESUMO
A cerebral gyrus is made up of an external layer of folded cortex and an inner core of white matter. The architecture of the core has specific features that make it distinct from the white matter of the deep brain regions. Limited externally by the grey matter that covers the top of the gyrus and the neighbouring sulci, this gyral white matter is made up of a mix of fibre populations with multiple directions and destinations. The presence of densely packed fibres with multiple crossings, the proximity to the cortex and the existence of inter-regional and inter-individual variations make the task of depicting this microanatomy extremely challenging. The topic is, however, of paramount relevance for both fundamental and applied neurosciences. This fibre colocalization is crucial for the functional role of each cerebral region and is key to clinical manifestations in cases of parenchymal damage. As track tracing, imaging and dissection are based on different biological or physical principles, it is natural for their results to sometimes be different, but they are often complementary. As the amount of available information increases, it becomes fragmented due to the multiplicity of methods, target phenomena and studied species. In this scoping review, we present the key concepts and map the primary sources of evidence regarding identifying the fibre pathways that compose the gyral white matter, enabling the discussion of avenues for future research. The general pattern in which these pathways are distributed in the gyral white matter was detailed, and the main variations as a function of brain topography were explained and illustrated with typical examples.
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Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d post-treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim based herbicide exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-based herbicide treated mice, the expression of Erß and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-based herbicide treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.
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Herbicidas , Gravidez , Animais , Feminino , Camundongos , Masculino , Herbicidas/toxicidade , Herbicidas/metabolismo , Proteômica , Sêmen , Testículo/metabolismo , Espermatozoides/metabolismo , Desenvolvimento EmbrionárioRESUMO
Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection (RET) gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the RET gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the RET gene result in Hirschsprung's disease.
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Polycystic ovarian syndrome (PCOS) is a complex health condition associated with metabolic disturbances and infertility. Recent data suggest that the prevalence of PCOS is increasing among women globally, although the etiology of these trends is undefined. Consequently, preclinical models that better reflect the biology of PCOS are urgently needed to facilitate research that can lead to the discovery of prevention strategies or improved management. The existing animal models have several limitations as they do not reflect all the PCOS features metabolically and/or phenotypically. Therefore, there is no clear consensus on the use of appropriate animal model and selection of the most appropriate PCOS-inducing agent. To that end, we have established a Swiss albino mouse model of PCOS based on 3 weeks of daily treatment with letrozole (50 µg/day; intraperitoneal) and dehydroepiandrosterone (DHEA, 6 mg/100 g body weight; subcutaneous) in 5-week-old female mice fed on normal or high-fat diet (HFD). Mice were regularly assessed for body weight, blood glucose, and estrous cycle. Three weeks after drug administration, mice were sacrificed and assessed for blood-based metabolic parameters as well as ovarian function. Our results indicate that DHEA combined with HFD produces changes mimicking those of clinical PCOS, including elevated serum testosterone and luteinizing hormone, dyslipidemia, poor ovarian microenvironment, and development of multiple ovarian cysts, recapitulating cardinal features of PCOS. In comparison, normal diet and/or letrozole produced fewer features of PCOS. The data from the experimental models presented here can improve our understanding of PCOS, a growing concern in women's health.
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Síndrome do Ovário Policístico , Animais , Peso Corporal , Desidroepiandrosterona , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Letrozol , Camundongos , Síndrome do Ovário Policístico/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: It has been documented that cardiac musculature is present in both venae cavae, and they contract together with the atrium, contributing to the pumping mechanism of the heart. So, in the present study, we measured the relative thicknesses of the three histological layers at formation, termination and intermediate levels of the venae cavae along with their histological characteristics. MATERIALS AND METHODS: Ten foetal and 10 adult cadavers were used. The Superior and Inferior Venae Cavae from all three regions were excised and processed for histology. The qualitative and quantitative features of the vessels were observed and recorded. The data thus obtained was then assessed statistically. RESULTS: In superior vena cava, the tunica intima grows actively especially during late gestation. The tunica media shows active growth. The tunica adventitia growth is significant at the middle and termination levels. In inferior vena cava, the tunica intima grows actively at the level of formation. The tunica media shows the active overall growth during early gestation. The tunica adventitia shows active growth during late gestation. In qualitative analysis the plump, spindle-shaped primitive mesenchymal cells were observed. Muscle and collagen fibers show reciprocal abundance with increasing age, with the former being lesser in amount than the latter in earlier stages. Appearance of vasa vasorum was notable from 2nd trimester. The cardiac myocytes were located in the middle and outer tunics of the superior vena cava. CONCLUSION: Cardiac musculature was absent in the inferior vena; however, the vessel shows advanced rate of overall development.
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Feto/irrigação sanguínea , Veia Cava Inferior/crescimento & desenvolvimento , Veia Cava Superior/crescimento & desenvolvimento , Veias Cavas/crescimento & desenvolvimento , Adulto , Cadáver , Coração/anatomia & histologia , Coração/crescimento & desenvolvimento , Humanos , Veia Cava Inferior/anatomia & histologia , Veia Cava Superior/anatomia & histologia , Veias Cavas/anatomia & histologiaRESUMO
Prepubertal Swiss albino mice of both sex were administered with first-line anti-tuberculosis drugs (ATDs) viz; rifampicin, isoniazid, pyrazinamide, streptomycin and ethambutol intraperitoneally, for 4 weeks. Two weeks after the completion of treatment, male mice were sacrificed to collect caudal spermatozoa and female mice were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to collect metaphase II (MII) oocytes from oviduct. Administration of ATDs not only decreased the count, motility and, nuclear maturity and also, increased the head abnormalities, mitochondrial damage and DNA damage in epididymal spermatozoa. Reduction in number of ovulated oocytes, increased degeneration rate and altered distribution pattern of cytoplasmic organelles was observed in oocytes of female mice. Presence of ATDs in in vitro maturation (IVM) medium increased abnormalities in meiotic resulted in abnormal spindle organization (except ethambutol) without affecting nuclear maturation. In conclusion, the result of this study indicates that ATDs have considerable adverse effects on the functional competence of male and female gametes, however, with varied degree of toxicity.
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Antituberculosos/toxicidade , Oócitos/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Núcleo Celular , Etambutol/toxicidade , Feminino , Isoniazida/toxicidade , Masculino , Metáfase , Camundongos , Preparações Farmacêuticas , Gravidez , Pirazinamida/toxicidade , Rifampina/toxicidade , Estreptomicina/toxicidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. is known for its nutritional and ethno medicinal values due to the presence of wide array of phytochemicals with multiple biological activities. We have previously reported that ethanolic extract of Moringa oleifera leaves (MOE) ameliorated cyclophosphamide (CP)-induced testicular toxicity and improved functional integrity of spermatozoa as well as spermatogenic cells. AIM OF THE STUDY: The present study was planned to investigate whether the mitigation of CP-induced testicular toxicity by MOE is mediated via modulation of endocrine profile, genes associated with function of different cell types and enhancement of DNA repair response in spermatogonial cells. MATERIALS AND METHODS: Adult Swiss albino mice (8 week) were injected with CP (100 mg/kg, one dose in a week for 3 weeks) and MOE (100 mg/kg, 5 doses in a week for 4 weeks) either alone or in combination intraperitoneally. At 35 day post CP injection (first dose), the functional characteristics such as count, motility, head morphology and DNA integrity were assessed in epididymal spermatozoa. Key reproductive hormones like testosterone, follicle stimulating hormone (FSH) and Inhibin B concentration were analyzed in serum and testis. In addition, mRNA expression of genes pertaining to the function of Leydig, Sertoli and spermatogonial cells as well as antioxidant enzymes were evaluated in the testis. To understand the DNA damage and repair process in germ cells, prepubertal (2 week) mice were administered with single dose of CP (200 mg/kg) and/or MOE (100 mg/kg) and analyzed for expression of DNA damage (γ-H2AX, P53 and Caspase3) and repair genes (Rad51 and Ku80) in isolated spermatogonial cells at various time points after treatment. RESULTS: CP administration resulted in decrease in count, motility and increase in morphological defects and DNA damage in spermatozoa. Testosterone level was marginally decreased while there was a significant increase in FSH (p < 0.001) and decrease in inhibin B (p < 0.05) observed in CP treated mice. Administration of MOE prior to CP, improved sperm functional characteristics, decreased FSH and increased inhibin B levels. Expression of Abp was down-regulated while Transferrin, Fshr and Gata4 (Sertoli cell specific genes) were up-regulated in testis treated with CP. Administration of CP down-regulated the expression of Oct4 and Ddx4 (Spermatogonia specific genes). MOE administration was shown to ameliorate CP-induced damage by modulating the expression of genes specific to Sertoli and spermatogenic cells. Furthermore, MOE treatment reduced CP-induced DNA damage as evident from lower percentage of γ-H2AX positive spermatogonial cells. CONCLUSION: Administration of MOE mitigated CP-induced testicular damage by improving blood and, intra-testicular hormonal milieu as well as modulating the expression of genes pertaining to Sertoli and spermatogonial cells.
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Expressão Gênica/efeitos dos fármacos , Moringa oleifera , Extratos Vegetais/farmacologia , Testículo/metabolismo , Animais , Ciclofosfamida , Dano ao DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Hormônio Foliculoestimulante/sangue , Histonas/metabolismo , Inibinas/metabolismo , Masculino , Camundongos , Folhas de Planta , Proteínas de Ligação a RNA/metabolismo , Células de Sertoli/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogônias/citologia , Espermatozoides/metabolismo , Testosterona/sangueRESUMO
BACKGROUND: Cyclophosphamide (CPA) is an anti-cancer drug, used in chemotherapy. This is a toxic drug which targets the cancer cells and also the normal cells of the body. The original compound is inactive in vitro and exercises its biologic action through metabolites, chiefly phosphoramide mustard. The objective is to study the harmful effects of this drug on liver and kidney tissues. METHODS: To study the effect of cyclophosphamide on histology of liver and kidney, 40 adult male mice were taken and divided into two groups: control and test. Those in the test group were injected with the drug at doses of 100, 200, 250 mg/kg body weight. They were then sacrificed on day 7, 28 and 42. The liver and kidney tissue was processed, sectioned and stained with Haematoxylin and Eosin. RESULTS: Pathological changes were seen in the tissue within 7 days in high doses and after 28 days in low doses. As the dosage and the days administered increased, the changes were prominently seen and widespread. Pathology ranging from mild infiltration to necrosis and finally cytolysis were seen in liver and kidney tissue. CONCLUSION: Our study has demonstrated the effect of a progressive increase in dosage of cyclophosphamide in albino mice, and pathological alterations were observed in histology of liver and kidney by sequentially increasing both the dosage and duration of treatment. Subsequently, regular monitoring of liver and kidney function tests in patients undergoing chemotherapeutic regimen with administration of ahepato and nephroprotective agent becomes vital.
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Ciclofosfamida/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Ciclofosfamida/farmacocinética , Relação Dose-Resposta a Droga , Nefropatias/etiologia , Nefropatias/patologia , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Necrose , Mostardas de Fosforamida/metabolismoRESUMO
Development of excellent curative therapy for most of the malignancies has resulted in a growing population of cancer survivors who are at increased risk for a variety of health problems including infertility. Therefore, fertility preservation has become an important issue during cancer treatment in recent years. Combination therapy with natural agents such as vitamins, antioxidants, dietary supplements, and plant products are considered as an attractive option to mitigate normal tissue toxicity imparted by chemotherapy. The aim of the present study was to explore the beneficial effect of hydroethanolic extract of Indian propolis (HEIP) on mitigating mitomycin C (MMC)-induced testicular damage and its mechanism of action. Healthy adult male mice were injected intraperitoneally with saline, MMC, HEIP and HEIP followed by MMC after 1h. The animals were dissected at 35days after various treatments to analyze testicular function. MMC administration resulted in significant reduction in testicular function in a dose-dependent manner at 35days after treatment which significantly improved by HEIP pre-treatment. At 24h after treatment, MMC induced significant increase in oxidative stress, γ-H2AX foci and expression of RAD51 and KU80 in testicular cells. Prior treatment with HEIP decreased the oxidative stress, reduced DNA damage and restored the testicular testosterone and inhibin B level. In conclusion, co-administration of Indian propolis extract may play a promising beneficial role in fertility preservation of males undergoing chemotherapy.
Assuntos
Antioxidantes/metabolismo , Dano ao DNA/efeitos dos fármacos , Mitomicina/toxicidade , Própole/farmacologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Animais , Dano ao DNA/fisiologia , Índia , Masculino , Camundongos , Própole/isolamento & purificação , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/patologiaRESUMO
BACKGROUND: Knowledge of testicular artery variations is vital to ensure that they are not neglected during a variety of different operative techniques, since damage can cause testicular atrophy. OBJECTIVES: The present study was therefore intended to identify variants in the origin and course of the testicular arteries. An attempt was made to classify the arteries based on their various origins. METHODS: This study examined 42 formalin-fixed cadavers of 40 to 70-year-old adult males. Variant origins of the testicular artery were identified and classified. Variations in the origin and course of the artery were colored, photographed, and documented. The distances between the origins of the testicular arteries and the mid-points of the origins of the renal arteries were measured. RESULTS: Testicular arteries were classified into four categories on the basis of origin. This variability was defined in relation to the renal and inferior mesenteric arteries. The mean distance between the origin of the testicular artery and the mid-point of the origin of the renal artery were 3.08 and 3.47 cm, on the right and left sides respectively. Variations were almost exclusively found on the left side. The variations observed included multiple arterial twigs forming the testicular artery, suprarenal arteries arising from the testicular artery, and testicular artery duplication. CONCLUSION: This study provides an insight into variations in the testicular artery and proposes a classification which could help surgeons during a variety of procedures on the male abdomen and pelvis.
CONTEXTO: O conhecimento de variações da artéria testicular é vital para assegurar que essas artérias não serão negligenciadas durante a realização de diferentes técnicas operatórias, já que qualquer dano poderia causar atrofia testicular. OBJETIVOS: Este estudo teve como objetivo identificar variações na origem e no trajeto das artérias testiculares. Foi feita uma tentativa de classificar as artérias com base em suas diferentes origens. MÉTODOS: Este estudo examinou 42 cadáveres de adultos do sexo masculino com idade entre 40 e 70 anos preservados em formol. As diferentes origens da artéria testicular foram identificadas e classificadas. Variações na origem e no trajeto da artérias foram coloridas, fotografadas e documentadas. Foram medidas as distâncias entre a origem das artérias testiculares e o ponto médio da origem das artérias renais. RESULTADOS: As artérias testiculares foram classificadas em quatro categorias com base em sua origem. Essa variabilidade foi definida com relação às artérias renal e mesentérica inferior. A distância média entre a origem da artéria testicular e o ponto médio da origem da artéria renal foi de 3,08 e 3,47 cm nos lados direito e esquerdo, respectivamente. As variações foram encontradas quase exclusivamente no lado esquerdo. As variações observadas incluíram múltiplos ramúsculos formando a artéria testicular, artérias suprarrenais surgindo a partir da artéria testicular, e duplicação da artéria testicular. CONCLUSÃO: Este estudo traz informações sobre variações da artéria testicular e propõe uma classificação que poderia ajudar os cirurgiões durante diferentes procedimentos realizados no abdome e na pelve de pacientes do sexo masculino.
RESUMO
The present study reports the effect of ethambutol (EMB) on testicular function. Prepubertal and adult male Swiss albino mice were treated with 40, 80, 160mg/kg body weight of EMB, intraperitoneally, every alternate day for 4 weeks. After 2 weeks gap, mice were sacrificed to collect caudal spermatozoa. EMB treatment resulted in a dose-dependent decrease in the testicular weight, sperm count and motility while the percentage of sperm with head abnormalities, immature chromatin (P<0.001) and DNA damage increased (P<0.01). In addition, EMB treatment resulted in significant depletion of glutathione (P<0.05-P<0.01) and histopathological abnormalities such as large cells, vacuolation of tubules and isolated colonies of spermatogenic cells were observed. Oct4, 17ß-Hsd and c-Kit mRNA was marginally elevated in EMB treated testes at the highest dose studied. In conclusion, the result of the present study indicates that EMB has adverse effect on testicular function and impairs the sperm functional competence.