Chronic consumption of contaminated feed with 2 4 dichlorophenoxyacetic acid (2 4 D) herbicide in rodents: effects on male reproductive health / Consumo crônico de ração contaminada com herbicida ácido 2 4 di clorofenoxiacético (2 4 D) em roedores: efeitos na saúde reprodutiva masculina

Introduction: The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most widely used pesticides in the world. There is evidence that this herbicide can induce deleterious effects in non-target organisms, including impairment of reproduction function. Objective: The aim of this study was to evaluate the reproductive effects of the chronic consumption of contaminated feed with 2,4-D in rats using food environmental spraying simulation. Methods: Animals orally exposed received nebulized chow with 2,4-D solution in different concentrations for 180 days: 0 (control - CG), 20.69 (LCG), 34.63 (MCG), or 51.66 ppm day−1 (HCG). Results: Sperm quality was impaired to 2,4-D. The percentage of sperm with progressive movement, number of sperm in the testis and daily sperm production were decreased in all exposed groups to the herbicide compared to CG. Sperm counts in the caput/corpus and cauda epididymis were reduced in MCG and HCG, and sperm transit time was delayed in the epididymis of LCG. There was a negative impact on sperm morphology and plasma membrane integrity in MCG and HCG, respectively. Germ cell exfoliation within the lumen of the seminiferous tubules and epithelial vacuolization in epididymis were found in the HCG. Conclusion: This is the first study to describe the negative impact on male reproductive morphophysiology after chronic exposure to 2,4-D using food nebulization in environmentally relevant concentrations, based on agronomic use of the herbicide. The reproductive injuries identified raise concerns about the impacts of wide population exposure to 2,4-D (AU).

Introdução: O herbicida 2,4- ácido diclorofenoxiacético (2,4-D) é um dos agrotóxicos mais utilizados no mundo. Há evidências de que este herbicida pode induzir efeitos deletérios em organismos não-alvo, incluindo prejuízo na função reprodutiva. Objetivo: O objetivo deste estudo foi avaliar os efeitos reprodutivos do consumo crônico de ração contaminada com 2,4-D em ratos, utilizando simulação de pulverização ambiental de alimentos. Métodos: Animais expostos oralmente receberam ração nebulizada com solução de 2,4-D em diferentes concentrações por 180 dias: 0 (controle - GC), 20,69 (LCG), 34,63 (MCG) ou 51,66 ppm dia−1 (HCG). Resultados: A qualidade espermática foi prejudicada pelo 2,4-D. A porcentagem de espermatozoides com movimento progressivo, número de espermatozoides no testículo e produção diária de espermatozoides foram menores em todos os grupos expostos ao herbicida, quando comparados ao GC. A contagem de espermatozoides na cabeça/corpo e cauda do epidídimo foi reduzida em MCG e HCG, e o tempo de trânsito espermático atrasou no epidídimo em LCG. Houve impacto negativo na morfologia espermática e na integridade da membrana plasmática em MCG e HCG, respectivamente. Esfoliação de células germinativas no lúmen dos túbulos seminíferos e vacuolização epitelial no epidídimo foram encontradas em HCG. Conclusão: Este é o primeiro estudo a descrever o impacto negativo na morfofisiologia reprodutiva masculina após exposição crônica ao 2,4-D, utilizando nebulização de alimentos em concentrações ambientalmente relevantes, com base no uso agronômico do herbicida. As lesões reprodutivas identificadas levantam preocupações sobre os impactos da ampla exposição da população ao 2,4-D (AU).

Saúde mental e ambientes restauradores urbanos em tempos de covid-19 / Mental health and urban restorative environments during the COVID-19 / Santé mentale et environnements urbains réparateurs pendant le Covid-19 / Salud mental y ambientes urbanos restaurativos en tiempos de Covid-19

Resumo A pandemia de covid-19 impactou significativamente o estilo de vida das pessoas em todo o mundo. Esta pesquisa visa discutir a influência dos ambientes restauradores urbanos na saúde mental em tempos de pandemia. Trata-se de uma pesquisa básica de abordagem qualitativa, feita por meio de pesquisa bibliográfica. Os dados que orientaram o estudo contribuíram para a fase descritiva dos fenômenos e sua relação com a necessidade de aprimorar tendências biofílicas. A pesquisa apontou fortes correlações entre meio ambiente natural, saúde mental e qualidade de vida da população urbana. A pandemia também nos faz refletir sobre o modo de vida nas cidades e a forma como tratamos as questões ambientais. Diante deste cenário, notabiliza-se a importância do espaço natural na contribuição para a saúde mental da população urbana, minimizando o aparecimento das doenças mentais e dos prejuízos causados na qualidade de vida, acentuados pelo covid-19.

Abstract The COVID-19 Pandemic significantly affected people's lifestyles around the world. This qualitative study discusses the influence of urban restorative environments on mental health in times of pandemic. Data was collected by means of bibliographic research, to describe the phenomena related to the need to improve biophilic tendencies. Results showed strong correlations between the natural environment, mental health and quality of life of the urban population. The pandemic also questions how we live in cities and the way we treat environmental issues. Given this scenario, the natural environmental contributes greatly to the mental health of the urban population, minimizing the onset of mental illnesses and the damage to quality of life, accentuated by COVID-19.

Résumé La pandémie Covid-19 a affecté de manière significative le mode de vie des gens. Cette étude qualitative traite de l'influence des environnements urbains réparateurs sur la santé mentale en période de pandémie. Les données ont étés collectées par le biais d'une recherche bibliographique, afin de décrire les phénomènes liés à la nécessité d'améliorer les tendances biophiliques. Les résultats ont montré de fortes corrélations entre l'environnement naturel, la santé mentale et la qualité de vie de la population urbaine. La pandémie remet également en question la façon dont nous vivons dans les villes et la manière dont nous traitons les questions environnementales. Dans ce scénario, l'environnement naturel contribue grandement à la santé mentale de la population urbaine, en minimisant l'apparition de maladies mentales et l'atteinte à la qualité de vie, accentués par le Covid-19.

Resumen La pandemia del Covid-19 ha tenido un impacto significativo en el estilo de vida de las personas en todo el mundo. Esta investigación busca discutir la relación de los ambientes restaurativos urbanos en la salud mental en tiempos de pandemia. Se trata de una investigación básica con enfoque cualitativo a través de una investigación bibliográfica. Los datos del estudio contribuyeron a la fase descriptiva de los fenómenos y su relación con la necesidad de mejorar las tendencias biofílicas. La investigación mostró fuertes correlaciones en cuanto a la importancia del ambiente natural, la salud mental y la calidad de vida de la población urbana. La pandemia también nos hace reflexionar sobre la forma de vida en las ciudades y la forma en que tratamos los temas ambientales. Ante este escenario, se destaca el espacio natural como importante para contribuir a la salud mental de la población urbana, minimizando la aparición de enfermedades mentales y los daños ocasionados a la calidad de vida agravados por el Covid-19.

Digital image processing: a useful tool in the analysis of lung injuries caused by chronic inhalation of agricultural herbicides.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used in agriculture to control various weeds. The objective of this study was to use the digital image processing method to identify alveolar lesions in the lungs of rats submitted to chronic 2,4-dichlorophenoxyacetic acid (2,4-D) inhalation exposure. We used forty adult male Wistar rats. The rats were divided into four groups: control group (CG), low concentration group (LCG), medium concentration group (MCG), and high concentration group (HCG). In a 6-month exposure period, we used two boxes connected to ultrasonic nebulizers for herbicide spraying. After this period, the rats were euthanized for the collection and study of lung tissue. For each image, counts of injuries and blisters were performed automatically using a methodology based on digital image processing techniques. For analysis of the results, an electronic database (Excel®) was created. We used the Pearson method for correlation analysis; values of p <0.05 were considered significant. In the evaluation of healthy alveoli, we recorded positive and significant correlations between analysis from a pathologist and computational analysis. In the evaluation of injured alveoli, we recorded a positive but non-significant correlation between analysis from a pathologist and computational analysis. These results show the effectiveness of digital image processing when evaluating alveolar integrity.

Sperm quality of rats exposed to difenoconazole using classical parameters and surface-enhanced Raman scattering: classification performance by machine learning methods.

Difenoconazole is a fungicide extensively used in agriculture. The aim of this study was to evaluate the effects of difenoconazole fungicide on the sperm quality of rats. Wistar rats were divided into four groups: control and exposed to 5 (D5), 10 (D10), or 50 mg-1 kg bw-1day (D50) of difenoconazole for 30 days, by gavage. Classical sperm parameters and surface-enhanced Raman scattering (SERS) were performed. Progressive motility, acrosomal integrity, and percentage of morphologically normal spermatozoa were reduced in the D10 and D50 groups in comparison with the control group. Sperm viability was reduced only in the D50 group. Sperm number in the testis and caput/corpus epididymis and daily sperm production were reduced in the three exposed groups. SERS measurements showed changes in the spectra of spermatozoa from D50 group, suggesting DNA damage. In addition, machine learning (ML) methods were used to evaluate the performance of three classification algorithms (artificial neural network-ANN, K-nearest neighbors-K-NN, and support vector machine-SVM) in the identification task of the groups exposed to difenoconazole. The results obtained by ML algorithms were very promising with accuracy ≥ 90% and validated the hypothesis of the exposure to difenoconazole reduces sperm quality. In conclusion, exposure of rats to different doses of the fungicide difenoconazole may impair sperm quality, with a recognizable classification pattern of exposure groups.

Performance of machine-learning algorithms to pattern recognition and classification of hearing impairment in Brazilian farmers exposed to pesticide and/or cigarette smoke.

The use of pesticides has been increasing in agriculture, leading to a public health problem. The aim of this study was to evaluate ototoxic effects in farmers who were exposed to cigarette smoke and/or pesticides and to identify possible classification patterns in the exposure groups. The sample included 127 participants of both sexes aged between 18 and 39, who were divided into the following four groups: control group (CG), smoking group (SG), pesticide group (PG), and smoking + pesticide group (SPG). Meatoscopy, pure tone audiometry, logoaudiometry, high-frequency thresholds, and immittance testing were performed. Data were evaluated by artificial neural network (ANN), K-nearest neighbors (K-NN), and support vector machine (SVM). There was symmetry between the right and left ears, an increase in the incidence of hearing loss at high frequency and of downward sloping audiometric curve configuration, and alteration of stapedial reflex in the three exposed groups. The machine-learning classifiers achieved good classification performance (control and exposed). The best classification results occur in high type (I and II) datasets (about 90% accuracy) in k-NN test. It is concluded that both xenobiotic substances have ototoxic potential; however, their combined use does not present additive or potentiating effects recognizable by the algorithms.

Experimental exposure to gasohol impairs sperm quality with recognition of the classification pattern of exposure groups by machine learning algorithms.

Contamination caused by leakage at gas stations leads to possible exposure of the general population when in contact with contaminated water and soil. The present study aimed to evaluate the reproductive effects of exposure of adult male rats to gasohol and evaluate the performance of machine learning (ML) algorithms for pattern recognition and classification of the exposure groups. Rats were orally exposed to 0 (control), 16 (EA), 160 (EB), or 800 mg kg-1 bw day-1 of gasohol (EC), for 30 consecutive days. Sperm quality of the groups exposed to two higher doses was reduced in comparison to the control group. The sperm parameters decreased were: daily sperm production, sperm number in the caput/corpus epididymis, progressive motility, mitochondrial activity, and acrosomal membrane integrity. Sperm transit time in the epididymis cauda and sperm isolated head were increased in EB and EC. Sertoli cells number was decreased in these groups, but their support capacity was maintained. ML methods were used to identify patterns between samples of control and exposure groups. The results obtained by ML methods were very promising, obtaining about 90% of accuracy. It was concluded that the exposure of rats to different doses of gasohol impair spermatogenesis and sperm quality, with a recognizable classification pattern of exposure groups at ML.

Avaliação da cavidade nasal de camundongos submetidos à exposição ao herbicida ácido 2, 4- diclorofenoxiacético / Evaluation of the nasal cavity mice submitted to the inhalation exposure to the herbicide 2, 4 - dichlorophenoxyacetic acid

No último ano, o Brasil apresentou um aumento de 190% na utilização de agrotóxicos, o que implica em um grave problema de saúde pública. O ácido 2,4-diclorofenoxiacético possui classificação toxicológica I (extremamente tóxico) e por ser muito volátil, favorece a contaminação de solos, águas, animais e seres humanos. Modelo do estudo: Estudo Experimental. Objetivo: Analisar o infiltrado inflamatório de camundongos submetidos à nebulização aguda ao herbicida ácido 2,4-diclorofenoxiacético, em diferentes intervalos de tempo e concentrações. Métodos: Foram utilizados 80 camundongos Swiss machos divididos em quatro grupos (n=20): salina, baixa (3,71 x 10-3 gramas de ingrediente ativo por hectare), média (6,19 x 10-3 gramas de ingrediente ativo por hectare) e alta concentração (9,28 x10-3 gramas de ingrediente ativo por hectare). Todos os animais foram expostos às nebulizações preconizadas para cada grupo por 15 minutos, em diferentes intervalos de tempo: 24, 48, 72 e 192 horas. O protocolo de exposição contou com duas caixas ligadas a um nebulizador ultrassônico e o vestíbulo nasal de cada animal foi retirado após a eutanásia, para a análise histológica. Resultados: A contagem de mastócitos apresentou valores significativamente aumentados no grupo alta concentração, no intervalo de tempo de 48 horas, quando comparado ao de 24 horas. Conclusão: Os resultados mostraram que a exposição aguda ao herbicida ácido 2,4-diclorofenoxiacético aumenta a produção de mastócitos na cavidade nasal de animais expostos a altas concentrações, e que podem estar relacionados ao surgimento de reações alérgicas. (AU)

In the last year, Brazil presented a 190% increase in the use of agrochemicals, which implies a serious public health problem. 2,4-Dichlorophenoxyacetic acid has toxicological classification I (extremely toxic) and because it is very volatile, it favors the contamination of soils, water, animals and humans. Study model: Experimental study. Objective: To analyze the inflammatory infiltrate of mice submitted to acute nebulization to the 2.4-dichlorophenoxyacetic acid herbicide at different time intervals and concentrations. Methods: Eighty Swiss male mice were divided into four groups (n=20): saline, low (3.71 x 10-3 grams of active ingredient per hectare), medium (6.19 x 10-3 grams of active ingredient per hectare) and high concentration (9.28 x 10-3 grams of active ingredient per hectare). All animals were exposed to the nebulizations proposed for each group, for 15 minutes, at different time intervals: 24, 48, 72 and 192 hours. The exposure protocol had two boxes attached to an ultrasonic nebulizer and the nasal vestibule of each animal was removed after euthanasia for histological analysis. Results: The mast cell count showed significantly increased values in the high concentration group, in the time interval of 48 hours, when compared to the 24-hour period. Conclusion: The results showed that the acute exposure to the herbicide 2,4-dichlorophenoxyacetic acid increases the production of mast cells in the nasal cavity of animals exposed to high concentrations, which may be related to the appearance of allergic reactions. (AU)

Evaluation of genotoxic effects in Brazilian agricultural workers exposed to pesticides and cigarette smoke using machine-learning algorithms.

Monitoring exposure to xenobiotics by biomarker analyses, such as a micronucleus assay, is extremely important for the precocious detection and prevention of diseases, such as oral cancer. The aim of this study was to evaluate genotoxic effects in rural workers who were exposed to cigarette smoke and/or pesticides and to identify possible classification patterns in the exposure groups. The sample included 120 participants of both sexes aged between 18 and 39, who were divided into the following four groups: control group (CG), smoking group (SG), pesticide group (PG), and smoking + pesticide group (SPG). Their oral mucosa cells were stained with Giemsa for cytogenetic analysis. The total numbers of nuclear abnormalities (CG = 27.16 ± 14.32, SG = 118.23 ± 74.78, PG = 184.23 ± 52.31, and SPG = 191.53 ± 66.94) and micronuclei (CG = 1.46 ± 1.40, SG = 12.20 ± 10.79, PG = 21.60 ± 8.24, and SPG = 20.26 ± 12.76) were higher (p < 0.05) in the three exposed groups compared to the GC. In this study, we considered several different classification algorithms (the artificial neural network, K-nearest neighbors, support vector machine, and optimum path forest). All of the algorithms displayed good classification (accuracy > 80%) when using dataset2 (without the redundant exposure type SPG). It is clear that the data form a robust pattern and that classifiers could be successfully trained on small datasets from the exposure groups. In conclusion, exposing agricultural workers to pesticides and/or tobacco had genotoxic potential, but concomitant exposure to xenobiotics did not lead to additive or potentiating effects.

Experimental exposure to 3 monochloropropane 1, 2 diol from the pre puberty causes damage in sperm production and motility in adulthood / Exposição experimental ao 3 monocloropropano 1, 2 diol, a partir da pré puberdade, causa alteração na produção e motilidade espermática na idade adulta

3-Monochloropropane-1,2-diol (3-MCPD) is a food contaminant that can be formed during the thermic processing of various foodstuffs. Studies of reproductive toxicology of 3-MCPD are mainly concentrated in the evaluation of possible insults caused by exposure of adult animals. However, the prepuberty might be a period of different susceptibility to chemicals. The aim of this study was to evaluate the effects on reproductive endpoints of the 3-MCPD-exposure prepubertal male rats. Wistar male rats were assigned to 4 groups: control and exposed to 2.5; 5 or 10 mg kg-1 day-1 of 3-MCPD for 30 days by gavage. Testis and epididymis were used for sperm counts and histology analysis. Sertoli cell number and dynamic of the spermatogenesis were evaluated. Sperm were collected from the vas deferens for evaluation of the sperm motility and morphology. Number of sperm with progressive movement, number of Sertoli cells and germ cells and relative daily sperm production were decreased in the groups exposed to 5 and 10 mg kg-1 day- 1 of 3-MCPD. Sperm morphology, testicular and epididymal histology were comparable among groups. Results show that 3-MCPD-exposure of rats from prepuberty might cause alterations in spermatogenesis and sperm maturation, similarly to exposure in adulthood.

3-monocloropropano-1,2-diol (3-MCPD) é um contaminante alimentar formado durante o processamento térmico de vários produtos. Estudos de toxicologia reprodutiva do 3-MCPD estão concentrados principalmente na avaliação de danos causados pela exposição de animais adultos. No entanto, a peri-puberdade pode ser um período de susceptibilidade diferente a produtos químicos. O objetivo deste estudo foi avaliar os efeitos reprodutivos da exposição de ratos machos pré-púberes ao 3-MCPD. Ratos Wistar machos foram divididos em quatro grupos: controle e expostos a 2,5; 5 ou 10 mg kg-1 dia-1 de 3-MCPD durante 30 dias, por gavagem. Os testículos e epidídimos foram usados para contagem espermática e análise histológica. Foram avaliados o número de células de Sertoli e a dinâmica da espermatogênese. Espermatozoides foram coletados a partir dos ductos deferentes para avaliação da motilidade e morfologia. O número de espermatozoides com movimento progressivo, o número de células de Sertoli e de células germinativas e a produção espermática foram reduzidos nos grupos expostos a 5 e 10 mg kg-1 dia-1 de 3-MCPD. A morfologia espermática e histologia testicular e epididimária foram semelhantes entre os grupos. Os resultados mostram que a exposição de ratos ao 3-MCPD, a partir da pré-puberdade, pode causar alterações na espermatogênese e na maturação espermática, de forma semelhante à exposição na idade adulta.

Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor / Toxicidade materna e fetal de ratas Wistar expostas ao herbicida metolacloro

Metolachlor is a selective pre-emergent herbicide widely used in agriculture to control weeds. The aim of this study was to evaluate the possible effects of metolachlor on reproductive performance of adult rats, as well as its teratogenic potential when administered during the period of organogenesis. Pregnant adult female rats were allocated into 4 experimental groups (n = 10 group-1), that received 0 (control); 150 (TA); 300 (TB); or 1000 mg kg-1 bw day-1 (TC) of metolachlor, by gavage, from the 6th to 15th gestational day (GD). There is reduction in the weight gain of the animals from TB and TC groups compared to the control group. Liver and placenta weights were reduced in TB and TC groups, respectively, while the percentage of post-implantation loss was increased in the TC group. There were no external malformations in either rat of the control or treated groups. However, an increased incidence of skeletal anomalies and visceral anomalies (especially in the urogenital system) was observed in TC group. These results demonstrate that exposure of pregnant rats to metolachlor can lead to signs of general toxicity, late embryonic losses and congenital anomalies.

O metolacloro é um herbicida seletivo de pré-emergência, amplamente usado na agricultura para controlar ervas daninhas. O objetivo deste estudo foi avaliar os possíveis efeitos do metolacloro sobre o desempenho reprodutivo de ratas adultas, bem como o seu potencial teratogênico quando administrado durante o período da organogênese. Ratas adultas prenhes foram divididas em quatro grupos experimentais (n = 10 grupo-1), que receberam 0 (controle); 150 (TA); 300 (TB); ou 1.000 mg kg-1 dia-1 (TC) do metolacloro, via gavagem, do sexto ao 15º dia de gestação (DG). Foi observada redução no ganho de peso dos animais dos grupos TB e TC em comparação ao grupo controle. Os pesos do fígado e placenta foram reduzidos nos grupos TB e TC, respectivamente, enquanto que a percentagem de perda pós-implantação foi aumentada no grupo TC. Não foram observadas malformações externas nos ratos dos grupos controle e tratados. No entanto, foi observado aumento da incidência de anomalias esqueléticas e anomalias viscerais (especialmente no sistema urogenital) no grupo TC. Estes resultados demonstram que a exposição de ratas prenhes ao metolacloro pode levar a sinais de toxicidade geral, perdas embrionárias tardias e anomalias congênitas.

Evaluation of testicular tissue of adult rats treated with cisplatin incorporated into the liposome.

Cisplatin (CPL) is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. However, it causes serious side effects, especially on reproduction. In order to reduce the undesirable effects caused by many drugs, liposomes have been used as a good system for drug delivery. The aim of this study was to investigate, for the first time, the effects of CPL incorporated into the dipalmitoyl phosphatidylcholine liposome (DPPC) on the testicular tissue of adult Wistar rats. The animals (n = 20) were distributed into four experimental groups: (a) control (distillated water); (b) liposome (DPPC, 1 mL), (c) cisplatin incorporated into liposome (CPL/DPPC), and (d) CPL (8 mg/kg body weight). The animals received a single intraperitoneal injection and were killed 10 days after each treatment for histopathological analysis of testes. The results showed that the testicular histomorphometric parameters in rats of DPPC and CPL/DPPC groups were similar to those of the control group. Meanwhile, rats of the CPL-treated group showed a variety of morphological alterations, including atrophy of seminiferous tubules and presence of multinucleated cells in the germinal epithelium. The incorporation of CPL into the liposome had no influence on the testicular weight or any other stereological parameters, but it was beneficial in maintaining the body weight of the animals. In conclusion, the liposome suppressed the cytotoxic effects caused by cisplatin in the testes of rats, suggesting a possible use in chemotherapy against cancer to reduce the side effects seen on reproduction.

Sperm quality in adult male rats exposed to cadmium in utero and lactation.

Recent studies indicate that several anomalies of the male reproductive system may be produced by acute or chronic exposure to chemical substances released into the environment, attributed to increased industrial development. Among these substances are trace metals such as cadmium (Cd). The aim of this study was to assess reproductive parameters in adult male rats whose mothers were exposed to Cd during pregnancy and lactation. For this, pregnant rats were divided into two experimental groups: treated rats, which received ad libitum cadmium acetate (CdAc) solution in distilled water (10 mg Cd/L), and control rats, which received sodium acetate (NaAc) solution in distilled water (equimolar to the CdAc). The results showed that the exposure to Cd in utero and through lactation adversely affected sperm quality of adult rats, as evidenced by compromised sperm morphology and motility and increased rate of cell death in testis.

Paternal treatment with cisplatin impairs reproduction of adult male offspring in rats.

This study evaluated the acute and persistent effects of paternal cisplatin-treatment on progeny. Wistar male rats (45 days old) were assigned into 2 groups. Control and cisplatin (CP: 1mg/kg-d, 5 days/week, for 3 weeks, ip.). Male rats at 66 (end of treatment, acute effects evaluation) and 140 days old (after recovery period, persistent effects evaluation) were mated with females. Fetal and post-natal developments of the offspring sired by treated-male mated in both ages were evaluated, including fertility of adult male offspring. No adverse effects in fetal development or puberty onset were seen in CP offspring. However, testicular descent was delayed and postnatal growth was impaired in these animals (acute effect). Moreover, seminal vesicle weight and epididymal sperm count from adult progeny were affected (acute effects) by paternal CP-exposure. The only persistent effect found was alterations in the spermatogenesis. We conclude that paternal CP-administration during peri-puberty affects reproductive endpoints of the progeny.

Persistent impairment of testicular histology and sperm motility in adult rats treated with Cisplatin at peri-puberty.

Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. This study evaluated the effects of peri-pubertal cisplatin administration on several reproductive end-points and the reversibility of these effects in adulthood. Peri-pubertal Wistar male rats (45 days old) were divided into two groups: control (saline 0.9%) and cisplatin (1 mg/kg/day, 5 days/week, for 3 weeks, i.p.). The study was conducted in two steps and evaluations were performed at ages of 66 (post-pubertal age) and 140 (adult age) days on: (i) organ weights, serum gonadotropins and testosterone levels, sperm counts, motility and morphology, testicular histomorphometry, spermatogenesis kinetics, Sertoli cell number and in situ detection of apoptotic germ cells and (ii) sexual behaviour, fertility and intratesticular testosterone. At the end of cisplatin therapy, rats showed reductions in sperm production and reserves, sperm with progressive movement, tubular diameter, intratesticular testosterone and fertility potential, but increased numbers of TUNEL-positive seminiferous tubules, immotile sperm and pre-implantation losses compared with control. Moreover, cisplatin-treated post-pubertal rats displayed impaired testicular histopathology and sexual behaviour. Serum gonadotropins and testosterone levels, sperm morphology, spermatogenesis kinetics and Sertoli cell number were comparable between experimental groups at both ages. Alterations found in post-puberty were recovered at adulthood, except for sperm motility and damage to testicular histology. The persistence of these cisplatin effects, despite the unaltered fertility after natural mating in rats, may have implications for reproductive function of young boys undergoing cancer therapy, given the lower reproductive efficiency in human beings compared with rats.

Morfometria e estereologia testicular de ratos adultos tratados com ciclofosfamida incorporada ao lipossoma / Testicular morphometry and stereology of adult rats treated with cyclophosphamide incorporated to the liposome

Lipossomas representam um benéfico sistema de transporte de fármacos que é utilizado em estudos clínicos para atuar como um veículo não tóxico, reduzindo os efeitos colaterais e aumentando a eficácia de agentes antitumorais. O objetivo deste estudo é investigar, por meio de parâmetros morfométricos e estereológicos, os efeitos da ciclofosfamida incorporada aos lipossomas, em testículos de ratos adultos. Como resultado, a incorporação do agente oncolítico aos lipossomas mostrou, em primeiro lugar, aumento no peso e volume testicular, assim como aumento no diâmetro e área dos túbulos seminíferos.Para o grupo tratado com ciclofosfamida incorporada aos lipossomas as diferenças nos volumes testicular e do parênquima mostraram-se não significativas em relação ao grupo controle.Os resultados indicam que a incorporação da droga ao lipossoma reduz os efeitos colaterais sobre a gônada masculina.