Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear

Exercício físico paterno : efeitos no desempenho físico e cognitivo da prole

A prática de exercício físico de mulheres nos períodos de preconcepção e gestação causa uma série de efeitos benéficos no desenvolvimento da prole. Pouco se sabe, no entanto, sobre a influência do exercício físico masculino sobre seus descendentes. Como a espermatogênese é um processo contínuo, as experiências de vida dos pais poderiam reprogramar o genoma dos espermatozoides por meio de processos epigenéticos, por exemplo, que poderiam interferir no desenvolvimento da prole. A presente dissertação tem como objetivo estudar essa hipótese. Examinamos os efeitos do exercício físico paterno sobre os seguintes parâmetros de desenvolvimento da prole: maturação corporal, desempenho cognitivo, expressão do BDNF muscular, no hipocampo e córtex frontal; e metilação global do DNA no hipocampo. Para tanto, ratos Wistar machos foram divididos em dois grupos: sedentários e exercitados. O protocolo de exercício físico consistiu de corrida na esteira por um período de 8 semanas. Após, os animais foram expostos às fêmeas em período fértil e não-treinadas. Os filhotes de ambos os grupos de pais foram submetidos a testes para avaliação do ganho de peso e medidas de crescimento, do primeiro dia pós-natal (P1) até o P21 A partir do P46, foram realizadas a medida indireta do consumo máximo de oxigênio e a avaliação da aprendizagem espacial e memória, até o P52. Os animais foram submetidos à eutanásia; os músculos dos membros posteriores, os testículos, as glândulas adrenais e a gordura gonadal foram pesados. Os resultados mostram que a prole de pais treinados e de não-treinados não diferem quanto às medidas físicas, desempenho físico, avaliação cognitiva e expressão do fator trófico. No entanto, houve uma diminuição significativa no peso dos testículos e da gordura gonadal na prole de pais treinados. O nível de metilação do DNA no hipocampo de filhos de pais exercitados apresentou uma diminuição, comparada ao grupo de filhos de pais sedentários. Esse resultado aponta para uma maior expressão gênica no grupo exercitado. Embora no presente estudo os mecanismos pelos quais o exercício paterno influencia o desenvolvimento da prole não tenham sido estabelecidos, reforça-se o papel essencial que a atividade física tem em um estilo de vida saudável e na prevenção de doenças, além de não gerar prejuízos ao desenvolvimento dos descendentes.The physical exercise of women in the pre-conception and gestation periods causes a series of beneficial effects on offspring development. Little is known, however, about the influence of male physical exercise on their offspring. As spermatogenesis is a continuous process, the life experiences of the fathers could reprogram the sperm genome by means of epigenetic processes, for example, which could interfere in the development of the offspring. The present dissertation aims to study this hypothesis. We examined the effects of paternal physical exercise on the following parameters of offspring development: body maturation, cognitive performance, hippocampus, cortex and muscle BDNF expression, and global DNA methylation in the hippocampus. Thus, male Wistar rats were divided into two groups: sedentary and exercised. The physical exercise protocol consisted of running on the treadmill for a period of 8 weeks. Afterwards, the animals were exposed to females at a fertile and untrained. The pups of both groups of parents were submitted to tests to evaluate the weight gain and growth measures from the first postnatal day (P1) to P21. From P46, the indirect measurement of maximum oxygen consumption and the evaluation of spatial learning and memory were made until P52 The animals were submitted to euthanasia; the muscles of the hindlimbs, the testicles, the adrenal glands and the gonadal fat were weighed. The results showed that the offspring of trained and untrained fathers did not differ in physical measures, physical performance, cognitive evaluation and trophic factor expression. However, there was a significant decrease in testicles weight and gonadal fat in the offspring of trained parents. The level of DNA methylation in the hippocampus of pups of exercised fathers presented a decrease, compared to the group of pups of sedentary fathers. This result points to a greater gene expression in the exercised group. Although in the present study the mechanisms by which paternal exercise influences the development of the offspring have not been established, the essential role that physical activity has in a healthy lifestyle and in the prevention of diseases is reinforced, and it does not cause the offspring development any harm as well

Exercício físico paterno : efeitos no desempenho físico e cognitivo da prole

A prática de exercício físico de mulheres nos períodos de preconcepção e gestação causa uma série de efeitos benéficos no desenvolvimento da prole. Pouco se sabe, no entanto, sobre a influência do exercício físico masculino sobre seus descendentes. Como a espermatogênese é um processo contínuo, as experiências de vida dos pais poderiam reprogramar o genoma dos espermatozoides por meio de processos epigenéticos, por exemplo, que poderiam interferir no desenvolvimento da prole. A presente dissertação tem como objetivo estudar essa hipótese. Examinamos os efeitos do exercício físico paterno sobre os seguintes parâmetros de desenvolvimento da prole: maturação corporal, desempenho cognitivo, expressão do BDNF muscular, no hipocampo e córtex frontal; e metilação global do DNA no hipocampo. Para tanto, ratos Wistar machos foram divididos em dois grupos: sedentários e exercitados. O protocolo de exercício físico consistiu de corrida na esteira por um período de 8 semanas. Após, os animais foram expostos às fêmeas em período fértil e não-treinadas. Os filhotes de ambos os grupos de pais foram submetidos a testes para avaliação do ganho de peso e medidas de crescimento, do primeiro dia pós-natal (P1) até o P21 A partir do P46, foram realizadas a medida indireta do consumo máximo de oxigênio e a avaliação da aprendizagem espacial e memória, até o P52. Os animais foram submetidos à eutanásia; os músculos dos membros posteriores, os testículos, as glândulas adrenais e a gordura gonadal foram pesados. Os resultados mostram que a prole de pais treinados e de não-treinados não diferem quanto às medidas físicas, desempenho físico, avaliação cognitiva e expressão do fator trófico. No entanto, houve uma diminuição significativa no peso dos testículos e da gordura gonadal na prole de pais treinados. O nível de metilação do DNA no hipocampo de filhos de pais exercitados apresentou uma diminuição, comparada ao grupo de filhos de pais sedentários. Esse resultado aponta para uma maior expressão gênica no grupo exercitado. Embora no presente estudo os mecanismos pelos quais o exercício paterno influencia o desenvolvimento da prole não tenham sido estabelecidos, reforça-se o papel essencial que a atividade física tem em um estilo de vida saudável e na prevenção de doenças, além de não gerar prejuízos ao desenvolvimento dos descendentes.The physical exercise of women in the pre-conception and gestation periods causes a series of beneficial effects on offspring development. Little is known, however, about the influence of male physical exercise on their offspring. As spermatogenesis is a continuous process, the life experiences of the fathers could reprogram the sperm genome by means of epigenetic processes, for example, which could interfere in the development of the offspring. The present dissertation aims to study this hypothesis. We examined the effects of paternal physical exercise on the following parameters of offspring development: body maturation, cognitive performance, hippocampus, cortex and muscle BDNF expression, and global DNA methylation in the hippocampus. Thus, male Wistar rats were divided into two groups: sedentary and exercised. The physical exercise protocol consisted of running on the treadmill for a period of 8 weeks. Afterwards, the animals were exposed to females at a fertile and untrained. The pups of both groups of parents were submitted to tests to evaluate the weight gain and growth measures from the first postnatal day (P1) to P21. From P46, the indirect measurement of maximum oxygen consumption and the evaluation of spatial learning and memory were made until P52 The animals were submitted to euthanasia; the muscles of the hindlimbs, the testicles, the adrenal glands and the gonadal fat were weighed. The results showed that the offspring of trained and untrained fathers did not differ in physical measures, physical performance, cognitive evaluation and trophic factor expression. However, there was a significant decrease in testicles weight and gonadal fat in the offspring of trained parents. The level of DNA methylation in the hippocampus of pups of exercised fathers presented a decrease, compared to the group of pups of sedentary fathers. This result points to a greater gene expression in the exercised group. Although in the present study the mechanisms by which paternal exercise influences the development of the offspring have not been established, the essential role that physical activity has in a healthy lifestyle and in the prevention of diseases is reinforced, and it does not cause the offspring development any harm as well

Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development

Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father’s life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20 min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant’s development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father’s contribution in fetal programming

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear

Severe uncontrolled maternal hyperglycemia induces microsomia and neurodevelopment delay accompanied by apoptosis, cellular survival, and neuroinflammatory deregulation in rat offspring hippocampus

Maternal diabetes constitutes an unfavorable intrauterine environment for offspring development. Although it is known that diabetes can cause brain alterations and increased risk for neurologic disorders, the relationship between neuroimmune activation, brain changes, and neurodevelopment deficits in the offspring remains unclear. In order to elucidate the short- and long-term biological basis of the developmental outcomes caused by the severe uncontrolled maternal hyperglycemia, we studied apoptosis, neurogenesis, and neuroinflammation pathways in the hippocampus of neonates and young rats born to diabetic dams. Diabetes was induced on gestational day 5 by an injection of streptozotocin. Evaluations of milestones, body growth, and inhibitory avoidance were performed to monitor the offspring development and behavior. Hippocampal modifications were studied through cellular survival by BrdU in the dentate gyrus, expression of apoptosis-regulatory proteins (procaspase 3, caspase 3, and Bcl-2), BDNF, and neuroinflammatory modulation by interleukins, MHC-I, MHC-II, Iba-1, and GFAP proteins. Severe maternal diabetes caused microsomia and neurodevelopmental delay in pups and decrease of Bcl-2, procaspase 3, and caspase 3 in the hippocampus. Moreover, in a later stage of development, it was found an increase of TNF-α and a decrease of procaspase 3, caspase 3, MHC-I, IL-1β, and BDNF in the hippocampus, as well as impairment in cellular survival in the dentate gyrus. This study showed significant short- and long-term commitments on the development, apoptosis, cell survival, and neuroinflammation in the offspring hippocampus induced by severe uncontrolled maternal hyperglycemia. The data reinforce the need for treatment of maternal hyperglycemic states during pregnancy and breast-feeding.Fil: Piazza, Francele Valente. Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saude; BrasilFil: Segabinazi Dumas, Maria Lucia. Universidade Federal do Rio Grande do Sul; BrasilFil: de Meireles, André Luís Ferreira. Universidade Federal do Rio Grande do Sul; BrasilFil: Mega, Filipe. Universidade Federal do Rio Grande do Sul; BrasilFil: Spindler, Christiano de Figueiredo. Universidade Federal do Rio Grande do Sul; BrasilFil: Augustin, Otávio Américo. Universidade Federal do Rio Grande do Sul; BrasilFil: Salvalaggio, Gabriela dos Santos. Universidade Federal do Rio Grande do Sul; BrasilFil: Achaval, Matilde. Universidade Federal do Rio Grande do Sul; BrasilFil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Marcuzzo, Simone. Universidade Federal do Rio Grande do Sul; Brasi