Navegando por Palavras-chave "spermatogenesis"

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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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    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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    The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition
    (Portland Press, 2005-01-01) Shin, Hwain; Renatus, Martin; Eckelman, Brendan P.; Nunes, Viviane Abreu [UNIFESP]; Sampaio, Claudio Augusto Machado [UNIFESP]; Salvesen, Guy S.; Burnham Inst; Univ Calif San Diego; Universidade Federal de São Paulo (UNIFESP)
    Several IAP (inhibitor of apoptosis) proteins regulate cell fate decisions, and the X-linked IAP (XIAP) does so in part by inhibiting caspases, proteases that execute the apoptotic pathway. A tissue-specific homologue of XIAP, known as ILP2 (IAP-like protein 2), has previously been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. in examining this protein we found that the putative caspase 9 interaction domain is a surprisingly weak inhibitor and is also conformationally unstable. Comparison with the equivalent domain in XIAP demonstrated that the instability is due to the lack of a linker segment N-terminal to the inhibitory BIR (baculovirus IAP repeat) domain. Fusion of a 9-residue linker from XIAP to the N-terminus of ILP2 restored tight caspase 9 inhibition, dramatically increased conformational stability and allowed crystallization of the ILP2 BIR domain in a form strikingly similar to the XIAP third BIR domain. We conclude that ILP2 is an unstable protein, and cannot inhibit caspase 9 in a physiological way on its own. We speculate that ILP2 requires assistance from unidentified cellular factors to be an effective inhibitor of apoptosis in vivo.
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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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    Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells
    (Soc Study Reproduction, 2000-11-01) Franca, L. R.; Leal, M. C.; Sasso-Cerri, E. [UNIFESP]; Vasconcelos, A.; Debeljuk, L.; Russell, L. D.; So Illinois Univ; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP)
    Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.
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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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    Is rainfall seasonality important for reproductive strategies in viviparous Neotropical pit vipers? A case study with Bothrops leucurus from the Brazilian Atlantic Forest
    (British Herpetol Soc, 2014-04-01) Barros, Veronica Alberto; Rojas, Claudio Augusto [UNIFESP]; Almeida-Santos, Selma Maria; Univ Estadual Paulista; Inst Butantan; Universidade Federal de São Paulo (UNIFESP)
    Two populations of the Neotropical lancehead Bothrops leucurus were studied in two locations in Brazil (Espirito Santo, ES, and Bahia, BA) with different rainfall seasonality patterns. The timing of reproduction was very similar in both populations, with the mating season occurring in autumn (when spermatozoa were found in uteri) and births occurring in summer. In males, spermatogenesis peaked in autumn, with evidence for increased secretory activity in the epithelium of the ductus deferens during the mating season in both populations. Our results indicate that phylogenetic inertia plays a major role in determining the timing of reproductive events in B. leucurus. However, snout-vent length (SVL) and clutch size were larger in individuals from BA than ES, which may be a result of differences in rainfall seasonality or other proximate factors (e.g., differential prey availability).
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    Reproductive Function of the Male Obese Zucker Rats: Alteration in Sperm Production and Sperm DNA Damage
    (Sage Publications Inc, 2014-02-01) Vendramini, V. [UNIFESP]; Cedenho, A. P. [UNIFESP]; Miraglia, S. M. [UNIFESP]; Spaine, D. M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Obesity has been considered a public health issue in many countries and is of increasing concern for authorities over the past 6 years. the Zucker rat is a good experimental model for obesity and diabetes studies due to its metabolic characteristics that are similar to those developed by humans. A total of 12 obese Zucker rats and their lean littermates were killed in pubertal and young adult phases for assessing organ weights (testis and epididymis), testicular histomorphometric and stereological analyses, daily sperm production, and transit time in the epididymis. Sperm integrity was also investigated in the adult animals using the Comet assay. Alterations in organ weights, seminiferous epithelium architecture, sperm production, and transit time were noticed in the pubertal fatty rats. the volume density of the lymphatic space was decreased in both the ages. Adult animals had a significant increase in the extent of damage found in sperm DNA. Our results show for the first time that leptin receptor deficiency compromises sperm production during puberty and that genetic obese Zucker rats have increased sperm DNA fragmentation.
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    Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B-12 efficacy in the recovery of spermatogonial germ cells
    (Wiley-Blackwell, 2016) Vasiliausha, Sandi Regina; Beltrame, Flavia Luciana [UNIFESP]; de Santi, Fabiane [UNIFESP]; Cerri, Paulo Sergio; Caneguim, Breno Henrique [UNIFESP]; Sasso-Cerri, Estela
    Several different strategies have been adopted in attempt to recover from chemotherapy-damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B-12 supplementation improves the haematological parameters and spermatogonia number. The animals received 10mg/kg of busulphan (BuG) or busulfan+vitamin B-12 (Bu/B(12)G) on the first and fourth days of treatment. In H.E.-stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E-stained and PCNA-immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL-positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B(12)G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B(12)G and BuG. In BuG, the number of H.E.-stained and PCNA-immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL-positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B(12)G, the number of H.E.-stained or PCNA-immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6days of busulphan exposure may be associated with the potential effect of this anti-neoplastic agent on SC. The increased number of spermatogonia in the busulphan-treated animals receiving vitamin B-12 indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients.
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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.
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    Vitamin B-12-induced spermatogenesis recovery in cimetidine-treated rats: effect on the spermatogonia number and sperm concentration
    (Medknow Publications & Media Pvt Ltd, 2017) Beltrame, Flavia L. [UNIFESP]; Sasso-Cerri, Estela
    The H-2-receptor antagonist cimetidine is an antiulcer drug also used for the treatment of cancer due to its antiangiogenic effect. However, this drug has caused structural changes in the seminiferous tubules. Vitamin B-12 has been used as a therapeutic agent for the treatment of male infertility. The supplementation of rats with vitamin B-12 during cimetidine treatment has recovered the damaged seminiferous tubules, but how this vitamin restores the seminiferous epithelium has not been clarified. In this study, we evaluated whether vitamin B-12 improves the number of spermatogonia, spermatocytes, and sperm concentration in cimetidine-treated rats. Adult male rats were treated for 50 days as follows: cimetidine group received 100 mg kg(-1) b.w. of cimetidine, cimetidine-B-12 group received cimetidine and 3 mu g of vitamin B-12-hydroxocobalamin, B-12 group received only 3 mu g of vitamin, and control group received saline. Sperm concentration was calculated and historesin-embedded testes sections were used for the quantitative analyses of spermatogonia (A