Navegando por Palavras-chave "testis"

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    Alterations of spermatogenesis in etoposide-treated rats: A stereological study
    (Interciencia, 2002-05-01) Freitas, Francisca Estela Lima [UNIFESP]; Mori, Flora Cordeiro [UNIFESP]|Sasso-Cerri, Estela [UNIFESP]; Lucas, Sandra Regina Rodrigues [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Acre; Univ Estadual Paulista
    The etoposide is an anticancer drug that interacts with topoisomerase II. Thirty-day-old rats received intraperitonially 2mg/kg of etoposide for 30 consecutive days. Their testes were analyzed in the adult phase under light microscopy according to histomorphometric and stereological parameters. Random 3mum-thick-paraplast sections of testis were stained with periodic acid-Schiff reaction and Harris' hematoxylin method. Serum testosterone level and reproductive performance were also investigated. The results showed an accentuated decrease in the frequency of germinal lineage cell types and differentiated spermatogonia were the most affected cell types. Morphometric and stereological testicular parameters exhibited highly, significant reductions in adult etoposide-treated rats. Their reproductive performance diminished but their serum testosterone level was not significantly altered. The mortality frequency of the progenies was 100%.
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    Amifostine protective effect on cisplatin-treated rat testis
    (Wiley-Blackwell, 2008-07-01) Lirdi, Leandra Campos [UNIFESP]; Stumpp, Taiza [UNIFESP]; Sasso-Cerri, Estela; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); São Paulo State Univ
    Cisplatin is a potent drug used in clinical oncology but causes spermatogenesis damage. Amifostine is a drug used against toxicity caused by ionizing irradiation and chemotherapeutic drugs. Since cisplatin provokes fertility and induces germ cell apoptosis and necrosis, we proposed to evaluate the amifostine cytoprotective action on testes of cisplatin-treated rats. Thirty-day-old prepubertal Wistar rats received a single cisplatin dose of 5 mg/kg and were killed after 3, 6, and 12 hr. the hematoxylin-eosin stained testicular sections were submitted to histological, morphometric, and stereological analysis. the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) method was used to label apoptotic cells. TUNEL-positive and TUNEL-negative germ cells with abnormal nuclear morphology (ANM) were scored. Significant alterations of greater part of the parameters occurred in the cisplatin-treated group (CE) compared to the group that received amifostine before the cisplatin-treatment (ACE); however, testicular weight and volume did not vary between these groups. Tubular diameter was reduced in CE in comparison to ACE rats, while interstitial tissue and lymphatic space volume and volume density were significantly higher in CE rats; interstitial testicular edema probably occurred in cisplatin-treated rats. CE rats showed important histological alterations, which were more accentuated than in ACE rats. the numerical densities of apoptotic germ cells and TUNEL-negative cells with ANM were lower in ACE than in CE rats. in conclusion, the amifostine previously administered to prepubertal rats reduced the testicular damage caused by cisplatin. We conclude that amifostine partially protected the rat seminiferous epithelium against cisplatin toxicity.
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    Androgens and the male reproductive tract: an overview of classical roles and current perspectives
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2009-11-01) Patrão, Marilia T. C. C. [UNIFESP]; Silva, Erick J. R. [UNIFESP]; Avellar, Maria Christina Werneck [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Androgens are steroid hormones that play key roles in the development and maintenance of male phenotype and reproductive function. These hormones also affect the function of several non-reproductive organs, such as bone and skeletal muscle. Endogenous androgens exert most of their effects by genomic mechanisms, which involve hormone binding to the androgen receptor (AR), a ligand-activated transcription factor, resulting in the modulation of gene expression. AR-induced non-genomic mechanisms have also been reported. A large number of steroidal and non-steroidal AR-ligands have been developed for therapeutic use, including the treatment of male hypogonadism (AR agonists) and prostate diseases (AR antagonists), among other pathological conditions. Here, the AR gene and protein structure, mechanism of action and AR gene homologous regulation were reviewed. The AR expression pattern, its in vivo regulation and physiological relevance in the developing and adult testis and epididymis, which are sites of sperm production and maturation, respectively, were also presented.
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    Apoptosis and testicular alterations in albino rats treated with etoposide during the prepubertal phase
    (Wiley-Blackwell, 2004-07-01) Stumpp, Taiza [UNIFESP]; Sasso-Cerri, Estela [UNIFESP]; Freymüller-Haapalainen, Edna [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Etoposide is a podophyllotoxin semiderivative that is used in a variety of chemotherapy treatments, including therapy for children tumors. This drug promotes the formation of a ternary DNA-topoisomerase II-etoposide complex that triggers apoptosis. the purpose of this work was to analyze the occurrence of apoptosis in the seminiferous epithelium of prepubertal, pubertal, and adult rats treated with 10, 20, and 40 mg/Kg of etoposide during the prepubertal phase, as well as the role of apoptosis in etoposide-induced testicular damage. the rat testes were fixed in Bouin's liquid, and the apoptotic cells were quantified by means of the hematoxylin and eosin (H&E) technique (all groups) and the terminal dUTP nick end labeling (TUNEL) method (prepubertal groups only). the results obtained from both the H&E and TUNEL methods showed an increased frequency of apoptosis in the seminiferous epithelium of treated animals, except for the subgroup that received the 10-mg/Kg dose and was sacrificed 12 hr after the treatment and for the etoposide-treated pubertal group, that did not show cells suggesting apoptosis during H&E analysis. the labeled cells were mainly primary spermatocytes and differentiated spermatogonia. the prepubertal rats showed an etoposide-dose-dependent diminution of differentiated spermatogonia. Etoposide treatment during the prepubertal phase increases the frequency of apoptosis in the seminiferous epithelium, and causes serious harm to male fertility. (C) 2004 Wiley-Liss, Inc.
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    Avaliação do tratamento crônico com resveratrol sobre níveis glicêmicos e parâmetros reprodutivos de ratos com diabetes tipo 1 induzida pela estreptozotocina na pré-puberdade
    (Universidade Federal de São Paulo (UNIFESP), 2014-12-18) Simas, Joana Nogueres [UNIFESP]; Valdeolivas, Sandra Maria Miraglia Valdeolivas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Aims/hypothesis: In Diabetes Mellitus, the persistent hyperglycemia unleashes the progression of several complications including the overproduction of reactive oxygen species and reproductive alterations. Resveratrol (RES) is antioxidant and antiapoptotic. We assessed the trilogy: type-1 Diabetes (DM1), male reproduction and RES-treatment. Methods: Eighty-four prepubertal male rats were distributed into 7 groups: sham-control (SC); RES-treated (R);resveratrol-vehicle-treated (RV); diabetic (D); diabetic-insulin-treated (DI); diabetic-RES-treated (DR), diabetic-insulin and RES-treated (DIR). DM1 was induced by a single intraperitoneal streptozotocin (STZ) injection (65 mg/kg) on the 30th day postpartum (dpp). Animals of DR, DIR and R groups received 150mg/day of RES by gavage for 42 consecutive days (from the 33 dpp). DI and DIR rats received subcutaneous injections of insulin (1U/100g bw/day) from the 5th day after the DM1 induction. The blood-glucose-measurement (BGM) of rats was obtained at 5 different time-points: before the STZ-treatment, at 33, 45, 64 and 75 dpp when they were submitted to euthanasia for morphometric and biometric testicular analyses, spermatic evaluation and hormonal dosages. Results: In the D group, BGM was higher than in DR, DI and DIR. Besides, morphometric testicular measurements and testosterone and estradiol dosages were lower than in DR and DIR; LH-dosage was also lower than in DR. The preputial-separation age was delayed in diabetes-induced groups. The DR and DIR groups showed an improvement of the sperm mitochondrial activity, epididymal sperm counts and of the frequency of morphologically normal sperms. Conclusions/interpretation: RES improved glycemia, sperm quantitative and qualitative parameters and hormonal profile in DM1-induced Rats.
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    Avaliação reprodutiva tardia da prole exposta à nicotina durante as fases de prenhez e lactação
    (Universidade Federal de São Paulo (UNIFESP), 2014-07-30) Silva, Mayra Miranda Rodrigues da [UNIFESP]; Valdeolivas, Sandra Maria Miraglia Valdeolivas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: About 1/3 of the population smokes. The nicotine found in cigarettes, reaches breast milk and crosses the placental membrane. Previously, it was observed that nicotine administered to female rats during pregnancy and lactation, causes morphofunctional alterations Leydig cells and overt damage of the seminiferous epithelium of the offspring. Objective: To evaluate the spermatogenic damage, previously observed in offspring at 90 days of age, from pregnant rats and exposed infants to nicotine, are held or aggravated after up to two full terms of spermatogenesis (53 + 53 days). Methods: Rats were exposed to nicotine (2 mg / kg / day) throughout pregnancy and lactation, using a subcutaneous osmotic minipump implantation (C) performed in each of these periods. Control groups "sham" (CS, with subcutaneously implanted minipumps, but containing 0.9% saline) and absolute (CA without implants) were established. The offspring were euthanized at 90, 143 and 196 days postpartum (subgroups). Testicular parameters, reviews and sperm and testosterone plasma levels and cholesterol intratesticular were investigated. Results: The progenies showed significant changes of biometric parameters, morphometric and stereological testicular, in all subgroups. Histopathology showed in rats of all subgroups nicotine, normal characteristics of the seminiferous epithelium, except for the more exacerbated peeling germ cells into the lumen, observed in these animals. Quantitative evaluation and sperm plasma levels and cholesterol and testosterone intratesticular no significant changes. However, the offspring of the subgroups nicotine exhibited high frequency of morphologically abnormal sperm and reduced sperm motility of these gametes. A significant loss of mitochondrial activity and an increase in sperm DNA fragmentation (comet assay) were observed in these animals. Conclusions: The results indicate reproductive harm late in the offspring, concerning the quality of the epididymal sperm tail, due to exposure of rats to nicotine in pregnancy and lactation.
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    Can selective retroperitoneal lymphadenectomy be better than unilateral retroperitoneal lymphadenectomy?
    (Sociedade Brasileira de Urologia, 2003-10-01) Arruda, Homero O. [UNIFESP]; Paula, Adriano A.p. [UNIFESP]; Suarez, Ruben [UNIFESP]; Cury, José [UNIFESP]; Srougi, Miguel [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: To propose a new modality of retroperitoneal lymphadenectomy as a complementary treatment for patients with high risk, stage I nonseminomatous testicular tumor. MATERIALS AND METHODS: We studied 76 patients with stage I nonseminomatous testis tumor (T1-T4, NX, M0) treated by orchiectomy and retroperitoneal lymphadenectomy. Among them, 33 patients underwent unilateral retroperitoneal lymphadenectomy (URL) and 43 selective retroperitoneal lymphadenectomy (SRL). URL consisted in removing the lymph nodes located around the great vessel homolateral to the tumor (aorta or vena cava and iliac vessels), and anterior and posterior to the contralateral great vessel (aorta or vena cava). SRL was performed removing the lymph nodes located anterior and between the great vessels (aorta or vena cava) and laterally to the homolateral great vessel, extending the distal dissection until the level of inferior mesenteric artery. In these groups of patients, the incidence of disease recurrence, disease-free survival index, and frequency of post-operative aspermia were assessed. Mean post-operative follow-up time was 96 months. RESULTS: In the SRL group there was only 5% of aspermia versus 79% in the URL group (p < 0.0001). Tumor recurrence was observed in only 5 of the 76 patients and was not related to the surgical technique. The disease-free survival rate after the mean follow-up of 96 months was similar in both groups, being 94% in the SRL group and 93% in the URL group. CONCLUSION: The selective retroperitoneal lymphadenectomy constitutes an effective technique with a lower morbidity than unilateral lymphadenectomy, representing an excellent option for the management of patients with high-risk, stage I nonseminomatous testis tumor.
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    Carbamazepine damage to rat spermatogenesis in different sexual developmental phases
    (Wiley-Blackwell, 2009-10-01) Oliva, Samara Urban de [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    P>Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also utilized for treatment of psychiatric disorders and neuropathic pain. the utilization of CBZ has been associated with damage to male reproduction including hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and long-term use of CBZ has been a common schedule for children and adolescents, despite the fact it alters the testosterone level in adult rats and humans. in addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and puberty is more susceptible to toxic agents than in adult phase. the objective of this work was to evaluate the side effects of CBZ on the spermatogenic process of rats from pre-puberty to puberty and sexual maturation. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and an increase in oestradiol levels were observed in rats, which were CBZ-treated since the weaning. the results suggest that CBZ, when administered from pre-puberty, provokes specific side effects on rat testes, resulting in more severe damage in the adult phase.
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    Clinical Outcome of Intracytoplasmic Sperm Injection in Infertile Men With Treated and Untreated Clinical Varicocele
    (Elsevier B.V., 2010-10-01) Esteves, Sandro C. [UNIFESP]; Oliveira, Fernanda V.; Bertolla, Ricardo P.; Universidade Federal de São Paulo (UNIFESP)
    Purpose: We evaluated the impact of varicocelectomy on intracytoplasmic sperm injection outcomes in infertile men with clinical varicocele.Materials and Methods: We studied 242 infertile men with a history of clinical varicocele who underwent intracytoplasmic sperm injection. of the men 80 underwent prior subinguinal microsurgical varicocelectomy (treated group 1) and 162 had any grade of clinical varicocele (untreated group 2) at sperm injection. We compared semen analysis results before and after varicocelectomy, and the sperm injection procedure outcomes. Mean time from surgery to sperm injection was 6.2 months. Logistic regression was done to verify whether varicocelectomy influenced the odds of clinical pregnancy, live birth and miscarriage.Results: We noted an improved total number of motile sperm (6.7 x 10(6) vs 15.4 x 10(6), p < 0.01) and a decreased sperm defect score (2.2 vs 1.9, p = 0.01) after vs before varicocele repair. the clinical pregnancy (60.0% vs 45.0%, p = 0.04) and live birth (46.2% vs 31.4%, p = 0.03) rates after the sperm injection procedure were higher in the treated than in the untreated group. the chance of achieving clinical pregnancy (OR 1.82; 95% CI 1.06-3.15) and live birth (OR 1.87, 95% CI 1.08-3.25) by the sperm injection procedure were significantly increased while the chance of miscarriage was decreased (OR 0.433, 95% CI 0.22-0.84) after varicocele was treated.Conclusions: Results suggest that varicocelectomy improves clinical pregnancy and live birth rates by intracytoplasmic sperm injection in infertile couples in which the male partner has clinical varicocele. the chance of miscarriage may be decreased if varicocele is treated before assisted reproduction.
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    Differential expression and antibacterial activity of epididymis protein 2 isoforms in the male reproductive tract of human and rhesus monkey (Macaca mulatta)
    (Soc Study Reproduction, 2004-11-01) Avellar, MCW [UNIFESP]; Honda, L. [UNIFESP]; Hamil, K. G.[UNIFESP]; Yenugu, S. [UNIFESP]; Grossman, G.; Petrusz, P.; French, F. S. [UNIFESP]; Hall, S. H. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ N Carolina
    The epididymis protein 2 (EP2) gene, the fusion of two ancestral P-defensin genes, is highly expressed in the epididymis and subject to species-specific regulation at the levels of promoter selection, transcription, and mRNA splicing. EP2 mRNA expression is also androgen dependent, and at least two of the secreted proteins bind spermatozoa. Alternative splicing produces more than 17 different EP2 mRNA variants. in this article, the expression of EP2 variants was profiled in different tissues from the human and rhesus monkey (Macaca mulatta) male reproductive tract using reverse transcriptase-polymerase chain reaction. Different EP2 mRNA variants were identified not only in human and rhesus testis and epididymis but also in the novel sites, seminal vesicle and prostate. Immunolocalization of EP2 protein in epithelial cells from rhesus and human seminal vesicle demonstrated that EP2 transcripts are translated in these tissues. in addition, two novel splicing variants, named EP2R and EP2S, were discovered. EP2C was the only splice variant expressed in all tissues tested from rhesus monkey. However, expression was not detected in human testis or seminal vesicle. for the first time, bactericidal function was demonstrated for EP2C, EP2K, and EP2L. Taken together, the results indicate that EP2 expression is more widespread in the male reproductive tract than realized previously. Whereas the activity of every EP2 variant tested thus far is antibacterial, further investigation may reveal additional physiological roles for EP2 peptides in the primate male reproductive tract.
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    Effects of prenatal and lactation nicotine exposure on rat testicular interstitial tissue
    (Wiley-Blackwell, 2014-03-01) Paccola, Camila Cicconi [UNIFESP]; Neves, F. M. O. [UNIFESP]; Cipriano, I. [UNIFESP]; Stumpp, Taiza [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Nicotine is largely consumed as a component of cigarettes. It induces apoptosis, interferes with endocrine function by changing the sex hormones secretion and leads to male infertility. Testosterone is produced from cholesterol by Leydig cells (LC), with the participation of testicular macrophages (MO). Thus, to investigate whether nicotine administration to pregnant and lactating rats changes cholesterol and sexual hormone levels and LC and MO populations of offspring, female rats received nicotine (2mg/kg/day) through osmotic minipumps from the first day of pregnancy up to the end of weaning. At 1, 30, 60 and 90days post-partum (dpp) the plasma cholesterol and testosterone levels were obtained, as well as the biometric, histopathological and stereological testicular parameters. Nicotine reduced the body weight, cholesterol levels and lipid droplet number in foetal LC at 1dpp. the number of apoptotic LC did not change in the offspring of nicotine group at any age studied. No alterations in the numerical densities of MO and LC occurred at 60 and 90dpp. Hypertrophy of mature LC and increase in cholesterol and testosterone levels were noted at 90dpp. in conclusion, nicotine when administered to rats throughout pregnancy and lactation induces morphofunctional alterations of foetal and mature LC and affects cholesterol and testosterone levels.
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    Evaluation of the tubular and interstitial functions of the testis in 46,XY patients with ambiguous genitalia
    (Freund Publishing House Ltd, 2000-06-01) Stuchi-Perez, E. Gabas; Lukas-Croisier, C.; De Castro, M.; Baptista, MT Matias; Scolfaro, M. Ribeiro; Marques-De-Faria, A. P.; Hackel, C.; Maciel-Guerra, A. T.; Guerra, G.; Universidade Estadual de Campinas (UNICAMP); Ecole Normale Super; Universidade Federal de São Paulo (UNIFESP)
    Investigation of the origin of sexual ambiguity is complex. Although testicular function has traditionally been assessed only by examining the steroidogenic capacity of Leydig cells and spermatogenesis, it has recently been shown that the measurement of serum anti-Mullerian hormone (AMH) as a marker of Sertoli cell function may also help clinicians. The aim of this study was to evaluate both Leydig and Sertoli cell functions in 46,XY patients with intersex states in order to establish biochemical patterns that would help to reach an etiologic diagnosis. We measured serum androgens, AMH and gonadotropins in 24 patients with sexual ambiguity and XY karyotype: 8 with gonadal dysgenesis (GD), 3 with 3 beta-hydroxy-steroid dehydrogenase deficiency (3 beta HSD), 5 with androgen insensitivity syndrome (AIS), 4 with 5 alpha-reductase 2 (SRD5A2) deficiency, and 4 were of unknown origin or idiopathic, Our results showed that while testosterone was low and gonadotropins elevated in patients with either GD or 3 beta HSD, AMH was low in the former and high in the latter. Serum AMH and gonadotropins were normal or high in patients with 3 beta HSD or AIS, but these could be distinguished by testosterone levels. Serum testosterone and gonadotropins were normal or high in AIS and SRD5A2 deficiency patients; however, while AMH was elevated in AIS, it was not the case in SRD5A2 deficiency patients, indicating that testosterone is sufficient to inhibit AMH within the testis. In idiopathic cases gonadotropins and testosterone were normal, and AMH was normal or low. We conclude that the combined measurement of androgens, AMH and gonadotropins helps to establish the diagnosis in intersex patients.
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    Histomorphometry of sexually immature albino rat testis after X ray-irradiation
    (Interciencia, 1997-03-01) Cabral, Maria das Gracas Botelho [UNIFESP]; Hayashi, Hisakazu [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    A A morphometric study was conducted of sexually immature albino rat testes which were exposed to a localized single. X-ray dose of 154.00 mC/Kg.The rats were killed at the ages of 25, 30, 35, 45, 60, 90 and 120 days. Their testes were removed from the scrota and examined microscopically by light microscope and macroscopically, To obtain better identification of all phases of spermatogenesis, 6 mu m-thick paraffin sections were stained using the periodic acid-Schiff (PAS) and Harris hematoxylin methods.The results show that X-rays provoke severe alterations in the seminiferous epithelium, selectively eliminating a significant quantity of the spermatogonia. On other hand, the elements which survived X-irradiation, including some types of spermatogonia and undifferentiated cells, were capable of repopulating the seminiferous epithelium. Animals irradiated at 25 days of age were found to be fertile when they were mated between 90 and 120 days.
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    Identification of a Critical Window for Ganciclovir-Induced Disruption of Testicular Development in Rats
    (Oxford Univ Press, 2018) Meyer, Katlyn Barp; Andrade, Anderson Joel Martino; Venturelli, Amanda Caroline; Kita, Diogo Henrique; Machado, Daria Louise Barbosa; Philipsen, Rafaela Adams; Silva, Alluanan Adelson do Nascimento; Cantao, Isabelle Hernandez [UNIFESP]; Moreira, Davyson de Lima; Silva, Valdemiro Amaro da; Stumpp, Taiza [UNIFESP]; Morais, Rosana Nogueira
    Ganciclovir (GCV) has been implicated in the development of testicular alterations. Exposure on gestational day (GD) 10 in rats induced permanent effects, including focal reduction or absence of germ cells (Sertoli cell-only tubules). Because the timing of exposure can be critical for testicular effects, we exposed rat dams to 300 mg/kg GCV (3 100 mg/kg subcutaneous injections) on GD10, 14 and 19, when germ cells have high rates of migration, proliferation and are mitotically quiescent, respectively. Males exposed to GCV in utero on GD10 and 14 were evaluated for androgenization markers, serum and fecal androgens, and testicular histomorphometry at adulthood. Double-labeling immunofluorescence for DAZL and Ki67 were used to assess gonocytes number and the proliferative activity of germ and somatic cells in fetal testes on GD15 and 20, ie, 24 h after GCV exposure. Adult rats exposed on GD14 showed delayed puberty onset, despite normal androgen levels. Also, there was a 50% reduction in testicular weight and about 30% of seminiferous tubules lacking germ cells. Effects on GD10 animals were less pronounced. In the fetal testis, the number of gonocytes was reduced by 50% in rats exposed on GD14, but normal in GD19 fetuses. GCV also reduced Sertoli cell proliferation immunolabeling in GD19 fetuses and Sertoli cell number in adults. In conclusion, GCV toxicity on germ cells seems to be linked to their proliferation rate and GD14 is a critical window in rats, when GCV exposure causes an acute massive loss of germ cells that persists until adulthood.
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    In situ demonstration of both TUNEL-labeled germ cell and Sertoli cell in the cimetidine-treated rats
    (F Hernandez, 2002-04-01) Sasso-Cerri, Estela [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Cimetidine has caused dysfunction in the male reproductive system. In the rat testis, intratubular alterations and loss of peritubular tissue due to peritubular myoid cell death by apoptosis have been recently shown. Thus, the aim of this study is to evaluate which cells of the seminiferous epithelium have been affected and/or died by apoptosis after the treatment with cimetidine.For this purpose, an experimental group containing five male albino Wistar rats received intraperitoneal injections of cimetidine (50 mg/kg body weight) during 52 days. The testes were fixed with 4% buffered formaldehyde and were embedded in paraffin, For detection of DNA breaks (apoptosis) in the cells of the seminiferous epithelium, the testicular sections were treated by the TUNEL method (Apop-Tag Plus Peroxidase Kit). In the tubules affected by cimetidine, altered peritubular tissue, including the presence of TUNEL labeling in the myoid peritubular cells, were usually found.In these tubules, the seminiferous epithelium exhibited low density of germ cells and TUNEL-positive labeling in the germ cells of the basal compartment. The concomitant staining in both germ cells of the basal compartment and late spermatids suggest a sensitivity of these cells in the damaged tubules. Besides germ cells, TUNEL-positive Sertoli cells were also found in the injured seminiferous tubules. Thus, a relationship between dying germ cells and Sertoli cell damage and/or death must be considered in tubules where peritubular tissue has been affected by toxicants.
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    Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation
    (Wiley-Blackwell, 2016) Miranda-Spooner, M. [UNIFESP]; Paccola, C. C. [UNIFESP]; Neves, F. M. O. [UNIFESP]; de Oliva, S. U. [UNIFESP]; Miraglia, S. M. [UNIFESP]
    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.
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    Monoclonality of asynchronous bilateral lymphoma of the testis
    (Karger, 2000-12-01) Leite, KRM; Garicochea, B.; Srougi, M.; Dzik, C.; Nesralhah, L.; Moura, R. P. de; Simpson, AJG; Darini, E.; Carvalho, C. M.; Camara-Lopes, L. H.; Sirio Libanes Hosp; Universidade Federal de São Paulo (UNIFESP); Hosp A C Camargo
    Objectives: Lymphoma is the most frequent testicular malignancy in men over 60 years of age. Even though patients present initially with localized disease, the high incidence of bilateral involvement, synchronous or not, and early systemic dissemination are characteristic of these neoplasms. Sometimes the interval between tumor involvement of both testes is long. the question is raised whether either the patient has a predisposition to present new clones of transformed lymphocytes, or the same disease using the same pathway from a systemic reservoir infiltrates the contralateral testis.Method: Polymerase chain reaction and DNA sequencing were used to detect immunoglobulin heavy chain (IgH) rearrangement in paraffin-embedded specimens from asynchronous tumors affecting the right and left testis of a 85-year-old man with an interval period of 13 months.Results: Both tumors showed the same IgH rearrangement.Conclusions.. the lymphoma affecting the left and right testis derived from the same clone. It makes a strong case that lymphoma of the testis is the first manifestation of a systemic disease and should be treated aggressively early at the beginning of the disease. Copyright (C) 2000 S. Karger AG. Basel.
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    Resveratrol attenuates reproductive alterations in type 1 diabetes-induced rats
    (Wiley, 2017) Simas, Joana Nogueres [UNIFESP]; Mendes, Talita Biude [UNIFESP]; Paccola, Camila Cicconi [UNIFESP]; Vendramini, Vanessa [UNIFESP]; Miraglia, Sandra Maria [UNIFESP]
    The progression of diabetes mellitus leads to several complications including overproduction of reactive oxygen species and reproductive alterations. As resveratrol (RES) is a powerful anti-oxidant and an anti-apoptotic compound, we hypothesized that side effects of type-1 diabetes (DM1) on male reproduction could be reduced by the RES treatment. Eighty-four prepubertal male rats were distributed into seven groups: sham control (SC), RES-treated (R), resveratrol-vehicle-treated (RV), diabetic (D), diabetic insulin-treated (DI), diabetic-RES-treated (DR), diabetic-insulin and RES-treated (DIR). DM1 was induced by a single intraperitoneal streptozotocin (STZ) injection (65 mg/kg) on the 30th day postpartum (dpp). Animals of DR, DIR and R groups received 150 mg/day of RES by gavage for 43 consecutive days (from the 33 to 75 dpp). DI and DIR rats received subcutaneous injections of insulin (1 U/100 g b.w./day) from 5th day after the DM1 induction. The blood glucose level was monitored. At 75 dpp, the euthanasia was performed for morphometric and biometric testicular analyses, spermatic evaluation and hormonal doses. In the I) group, the blood glucose level was higher than in the DR, DI and DIR groups. Besides morphometric testicular measurements, testosterone and estradiol doses were lower in I) group than in DR and DIR groups; LH dose was also lower than in DR. The preputial separation age was delayed in diabetes-induced groups. The DR and DIR groups showed an improvement in sperm mitochondrial activity, epididymal sperm counts and the frequency of morphologically normal sperms. RES treatment improved glycaemic level, sperm quantitative and qualitative parameters and the hormonal profile in DM1-induced rats and seems to be a good reproductive protector.
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    Sertoli cell function in albino rats treated with etoposide during prepubertal phase
    (Springer, 2006-09-01) Stumpp, Taiza [UNIFESP]; Freymuller, Edna; Miraglia, Sandra Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Sertoli cell plays a key role in spermatogenesis. Many studies refer that this cell is not harmed by the majority of anticancer treatments known to cause damage to the testis. However, in the previous study we observed that etoposide, an efficient chemotherapeutic drug, provokes an increase in numerical density of the Sertoli cells. This phenomenon suggests that this cell was harmed by etoposide. Thus, we decided to investigate a possible direct action of etoposide on Sertoli cells analyzing the function of this cell and relating it with the integrity and damage of the seminiferous epithelium. Prepubertal albino rats received 5 mg/kg of etoposide for eight consecutive days and were sacrificed in different ages. the control groups received 0.9% saline solution. the testes were fixed in Bouin's liquid for transferrin immunolabeling and testicular labeled tissue volume density measurement. Except for the younger rats, all the etoposide-treated rats showed diminution of transferrin immunolabeling in the seminiferous epithelium, and consequently, of total labeled testicular tissue volume density. We concluded that the diminution of transferrin labeling in the seminiferous epithelium was not associated with germ cell absence such as commonly reported. the results suggest etoposide impairs Sertoli cell function.
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    Sertoli cell morphological alterations in albino rats treated with etoposide during prepubertal phase
    (Cambridge Univ Press, 2008-06-01) Stumpp, Taiza [UNIFESP]; Freymuller, Edna [UNIFESP]; Miraglia, Sandra M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Sertoli cells are very important to spermatogenesis homeostasis because they control germ cell proliferation, differentiation, and death. Damages to Sertoli cells cause germ cell death and affect fertility. Etoposide is a potent chemotherapeutic drug largely used against a variety of cancers. However, this drug also kills normal cells, especially those undergoing rapid proliferation. in the testis, etoposide acts predominantly on intermediate and type B spermatogonia. Etoposide was shown to permanently alter Sertoli cell function when administered to prepubertal rats. Based on this, we decided to investigate whether etoposide can affect Sertoli cell morphology. for this, 25-day-old rats were treated with etoposide during 8 consecutive days and killed at 32, 45, 64, 127, and 180 days old. Testes were fixed in Bonin's liquid or in a mixture of 2.5% glutaraldehyde and 2% formaldehyde for analysis under light and electron microscopes, respectively. Sertoli cells showed morphological alterations such as the presence of chromatin clumps close to the nuclear membrane, nucleus displacement, and cytoplasmic vacuolization. Some Sertoli cells also showed nuclear and cytoplasmic degenerative characteristics, suggesting that etoposide causes severe damages to Sertoli cell.