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The neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett syndrome (RTT) patients. However, RTT is caused by MECP2 mutations whereas mutations in the TCF4 gene lead to PTHS. The mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists. We reprogrammed patient skin derived fibroblasts into induced neuronal progenitor cells. Interestingly, we discovered that MeCP2 levels were decreased in PTHS patient iNPCs relative to healthy controls and that both iNPCs and iAstrocytes displayed defects in function and differentiation in a mutation-specific manner. When Tcf4+/- mice were genetically crossed with mice overexpressing MeCP2, molecular and phenotypic defects were significantly ameliorated, underlining and important role of MeCP2 in PTHS pathology. Importantly, post-natal intracerebroventricular gene replacement therapy with adeno-associated viral vector serotype 9 (AAV9)-expressing MeCP2 (AAV9.P546.MeCP2) significantly improved iNPC and iAstrocyte function and effectively ameliorated histological and behavioral defects in Tcf4+/- mice. Combined, our data suggest a previously unknown role of MeCP2 in PTHS pathology and common pathways that might be affected in multiple neurodevelopmental disorders. Our work highlights potential novel therapeutic targets for PTHS, including upregulation of MeCP2 expression or its downstream targets or, potentially, MeCP2-based gene therapy.
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Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the X chromosome-linked gene Methyl-CpG Binding Protein 2 (MECP2). Restoring MeCP2 expression after disease onset in a mouse model of RTT reverses phenotypes, providing hope for development of treatments for RTT. Translatable biomarkers of improvement and treatment responses have the potential to accelerate both preclinical and clinical evaluation of targeted therapies in RTT. Studies in people with and mouse models of RTT have identified neurophysiological features, such as auditory event-related potentials, that correlate with disease severity, suggesting that they could be useful as biomarkers of disease improvement or early treatment response. We recently demonstrated that treatment of RTT mice with a positive allosteric modulator (PAM) of muscarinic acetylcholine subtype 1 receptor (M1) improved phenotypes, suggesting that modulation of M1 activity is a potential therapy in RTT. To evaluate whether neurophysiological features could be useful biomarkers to assess the effects of M1 PAM treatment, we acutely administered the M1 PAM VU0486846 (VU846) at doses of 1, 3, 10 and 30 âmg/kg in wildtype and RTT mice. This resulted in an inverted U-shaped dose response with maximal improvement of AEP features at 3 âmg/kg but with no marked effect on basal EEG power or epileptiform discharges in RTT mice and no significant changes in wildtype mice. These findings suggest that M1 potentiation can improve neural circuit synchrony to auditory stimuli in RTT mice and that neurophysiological features have potential as pharmacodynamic or treatment-responsive biomarkers for preclinical and clinical evaluation of putative therapies in RTT.
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Herein, we report on the further chemical optimization of the first reported mGlu7 positive allosteric modulator (PAM), VU6027459. Replacement of the quinoline core by a cinnoline scaffold increased mGlu7 PAM potency by â¼ 10-fold, and concomitant introduction of a chiral tricyclic motif led to potent mGlu7 PAMs with enantioselective mGlu receptor selectivity profiles. Of these, VU6046980 emerged as a putative in vivo tool compound with excellent CNS penetration (Kp = 4.1; Kp,uu = 0.7) and efficacy in preclinical models. However, either off-target activity at the sigma-1 receptor or activity at a target not elucidated by large ancillary pharmacology panels led to sedation not driven by activation of mGlu7 (validated in Grm7 knockout mice). Thus, despite a significant advance, a viable mGlu7 PAM in vivo tool remains elusive.
Assuntos
Regulação Alostérica , Camundongos , AnimaisRESUMO
Rett syndrome (RTT) and MECP2 Duplication syndrome (MDS) have opposing molecular origins in relation to expression and function of the transcriptional regulator Methyl-CpG-binding protein 2 (MeCP2). Several clinical and preclinical phenotypes, however, are shared between these disorders. Modulation of MeCP2 levels has recently emerged as a potential treatment option for both of these diseases. However, toxicity concerns remain with these approaches. Here, we focus on pharmacologically modulating the group II metabotropic glutamate receptors (mGlu), mGlu2 and mGlu3, which are two downstream targets of MeCP2 that are bidirectionally affected in expression in RTT patients and mice (Mecp2Null/+) versus an MDS mouse model (MECP2Tg1/o). Mecp2Null/+ and MECP2Tg1/o animals also exhibit contrasting phenotypes in trace fear acquisition, a form of temporal associative learning and memory, with trace fear deficiency observed in Mecp2Null/+ mice and abnormally enhanced trace fear acquisition in MECP2Tg1/o animals. In Mecp2Null/+ mice, treatment with the mGlu2/3 agonist LY379268 reverses the deficit in trace fear acquisition, and mGlu2/3 antagonism with LY341495 normalizes the abnormal trace fear learning and memory phenotype in MECP2Tg1/o mice. Altogether, these data highlight the role of group II mGlu receptors in RTT and MDS and demonstrate that both mGlu2 and mGlu3 may be potential therapeutic targets for these disorders.
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Deficiência Intelectual Ligada ao Cromossomo X , Receptores de Glutamato Metabotrópico , Síndrome de Rett , Animais , Modelos Animais de Doenças , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Glutamato Metabotrópico/metabolismo , Síndrome de Rett/tratamento farmacológico , Síndrome de Rett/genética , Síndrome de Rett/metabolismoRESUMO
The metabotropic glutamate receptor 7 (mGlu7) is a G protein-coupled receptor that has been recently linked to neurodevelopmental disorders. This association is supported by the identification of GRM7 variants in patients with autism spectrum disorder, attention deficit hyperactivity disorder, and severe developmental delay. One GRM7 mutation previously reported in 2 patients results in a single amino acid change, I154T, within the mGlu7 ligand-binding domain. Here, we report 2 new patients with this mutation who present with severe developmental delay and epilepsy. Functional studies of the mGlu7-I154T mutant reveal that this substitution resulted in significant loss of mGlu7 protein expression in HEK293A cells and in mice. We show that this occurred posttranscriptionally at the level of protein expression and trafficking. Similar to mGlu7-global KO mice, mGlu7-I154T animals exhibited reduced motor coordination, deficits in contextual fear learning, and seizures. This provides functional evidence that a disease-associated mutation affecting the mGlu7 receptor was sufficient to cause neurological dysfunction in mice and further validates GRM7 as a disease-causing gene in the human population.
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Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Fenótipo , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Criança , Pré-Escolar , Epilepsia , Medo , Feminino , Proteínas de Ligação ao GTP , Humanos , Lactente , Aprendizagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Transtornos do Neurodesenvolvimento/genética , Linhagem , ConvulsõesRESUMO
Allergic airway disease models use laboratory mice housed in highly controlled and hygienic environments, which provide a barrier between the mice and a predetermined list of specific pathogens excluded from the facility. In this study, we hypothesized that differences in facility barrier level and, consequently, the hygienic quality of the environment that mice inhabit impact the severity of pulmonary inflammation and lung function. Allergen-naive animals housed in the cleaner, high barrier (HB) specific pathogen-free facility had increased levels of inflammatory cytokines and higher infiltration of immune cells in the lung tissue but not in the bronchoalveolar lavage compared with mice housed in the less hygienic, low barrier specific pathogen-free facility. In both genders, house dust mite-induced airway disease was more severe in the HB than the low barrier facility. Within each barrier facility, female mice developed the most severe inflammation. However, allergen-naive male mice had worse lung function, regardless of the housing environment, and in the HB, the lung function in female mice was higher in the house dust mite model. Severe disease in the HB was associated with reduced lung microbiome diversity. The lung microbiome was altered across housing barriers, gender, and allergen-exposed groups. Thus, the housing barrier level impacts microbial-driven disease and gender phenotypes in allergic asthma. The housing of laboratory mice in more clean HB facilities aggravates lung immunity and causes a more severe allergic lung disease.
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Poeira/imunologia , Habitação , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Animais , Asma/etiologia , Citocinas/biossíntese , Feminino , Imunoglobulina E/sangue , Pulmão/imunologia , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hipersensibilidade Respiratória/etiologia , Fatores SexuaisRESUMO
Glucocorticoids (GC) are the mainstay treatment option for inflammatory conditions. Despite the broad usage of GC, the mechanisms by which GC exerts its effects remain elusive. Here, utilizing murine autoimmune and allergic inflammation models, we report that Foxp3+ regulatory T (Treg) cells are irreplaceable GC target cells in vivo. Dexamethasone (Dex) administered in the absence of Treg cells completely lost its ability to control inflammation, and the lack of glucocorticoid receptor in Treg cells alone resulted in the loss of therapeutic ability of Dex. Mechanistically, Dex induced miR-342-3p specifically in Treg cells and miR-342-3p directly targeted the mTORC2 component, Rictor. Altering miRNA-342-3p or Rictor expression in Treg cells dysregulated metabolic programming in Treg cells, controlling their regulatory functions in vivo. Our results uncover a previously unknown contribution of Treg cells during glucocorticoid-mediated treatment of inflammation and the underlying mechanisms operated via the Dex-miR-342-Rictor axis.
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Dexametasona/farmacologia , Glucocorticoides/farmacologia , Inflamação/tratamento farmacológico , MicroRNAs/genética , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Linfócitos T Reguladores/imunologia , Animais , Anti-Inflamatórios/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/biossíntese , Receptores de Glucocorticoides/genética , Linfócitos T Reguladores/metabolismoRESUMO
Inducible nitric oxide synthase (iNOS) and arginase-2 (ARG2) share a common substrate, arginine. Higher expression of iNOS and exhaled NO are linked to airway inflammation in patients. iNOS deletion in animal models suggests that eosinophilic inflammation is regulated by arginine metabolism. Moreover, ARG2 is a regulator of Th2 response, as shown by the development of severe eosinophilic inflammation in ARG2-/- mice. However, potential synergistic roles of iNOS and ARG2 in asthma have not been explored. Here, we hypothesized that arginine metabolic fate via iNOS and ARG2 may govern airway inflammation. In an asthma cohort, ARG2 variant genotypes were associated with arginase activity. ARG2 variants with lower arginase activity, combined with levels of exhaled NO, identified a severe asthma phenotype. Airway inflammation was present in WT, ARG2-/-, iNOS-/-, and ARG2-/-/iNOS-/- mice but was greatest in ARG2-/-. Eosinophilic and neutrophilic infiltration in the ARG2-/- mice was abrogated in ARG2-/-/iNOS-/- animals. Similarly, angiogenic airway remodeling was greatest in ARG2-/- mice. Cytokines driving inflammation and remodeling were highest in lungs of asthmatic ARG2-/- mice and lowest in the iNOS-/-. ARG2 metabolism of arginine suppresses inflammation, while iNOS metabolism promotes airway inflammation, supporting a central role for arginine metabolic control of inflammation.
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Arginase/metabolismo , Arginina/metabolismo , Inflamação/metabolismo , Pulmão/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Adulto , Animais , Arginase/genética , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Genótipo , Humanos , Inflamação/imunologia , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The ß-adrenergic receptor (ßAR) exists in an equilibrium of inactive and active conformational states, which shifts in response to different ligands and results in downstream signaling. In addition to cAMP, ßAR signals to hypoxia-inducible factor 1 (HIF-1). We hypothesized that a ßAR-active conformation (R**) that leads to HIF-1 is separable from the cAMP-activating conformation (R*) and that pulmonary arterial hypertension (PAH) patients with HIF-biased conformations would not respond to a cAMP agonist. We compared two cAMP agonists, isoproterenol and salbutamol, in vitro. Isoproterenol increased cAMP and HIF-1 activity, while salbutamol increased cAMP and reduced HIF-1. Hypoxia blunted agonist-stimulated cAMP, consistent with receptor equilibrium shifting toward HIF-activating conformations. Similarly, isoproterenol increased HIF-1 and erythropoiesis in mice, while salbutamol decreased erythropoiesis. ßAR overexpression in cells increased glycolysis, which was blunted by HIF-1 inhibitors, suggesting increased ßAR leads to increased hypoxia-metabolic effects. Because PAH is also characterized by HIF-related glycolytic shift, we dichotomized PAH patients in the Pulmonary Arterial Hypertension Treatment with Carvedilol for Heart Failure trial (NCT01586156) based on right ventricular (RV) glucose uptake to evaluate ßAR ligands. Patients with high glucose uptake had more severe disease than those with low uptake. cAMP increased in response to isoproterenol in mononuclear cells from low-uptake patients but not in high-uptake patients' cells. When patients were treated with carvedilol for 1 wk, the low-uptake group decreased RV systolic pressures and pulmonary vascular resistance, but high-uptake patients had no physiologic responses. The findings expand the paradigm of ßAR activation and uncover a novel PAH subtype that might benefit from ß-blockers.
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Hipertensão Pulmonar Primária Familiar/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Hipertensão Arterial Pulmonar/fisiopatologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Hipóxia/tratamento farmacológico , Isoproterenol/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Hipertensão Arterial Pulmonar/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Protease-activated receptor 2 (PAR-2), an airway epithelial pattern recognition receptor (PRR), participates in the genesis of house dust mite-induced (HDM-induced) asthma. Here, we hypothesized that lung endothelial cells and proangiogenic hematopoietic progenitor cells (PACs) that express high levels of PAR-2 contribute to the initiation of atopic asthma. HDM extract (HDME) protease allergens were found deep in the airway mucosa and breaching the endothelial barrier. Lung endothelial cells and PACs released the Th2-promoting cytokines IL-1α and GM-CSF in response to HDME, and the endothelium had PAC-derived VEGF-C-dependent blood vessel sprouting. Blockade of the angiogenic response by inhibition of VEGF-C signaling lessened the development of inflammation and airway remodeling in the HDM model. Reconstitution of the bone marrow in WT mice with PAR-2-deficient bone marrow also reduced airway inflammation and remodeling. Adoptive transfer of PACs that had been exposed to HDME induced angiogenesis and Th2 inflammation with remodeling similar to that induced by allergen challenge. Our findings identify that lung endothelium and PACs in the airway sense allergen and elicit an angiogenic response that is central to the innate nonimmune origins of Th2 inflammation.
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Alérgenos/imunologia , Asma/etiologia , Imunidade Inata , Pulmão/imunologia , Remodelação das Vias Aéreas/imunologia , Alérgenos/administração & dosagem , Animais , Asma/imunologia , Citocinas/biossíntese , Modelos Animais de Doenças , Fatores de Transcrição de Resposta de Crescimento Precoce/imunologia , Células Endoteliais/imunologia , Células Endoteliais/ultraestrutura , Feminino , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/patologia , Fatores de Transcrição Kruppel-Like/imunologia , Pulmão/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Neovascularização Patológica , Pyroglyphidae/imunologia , Receptor PAR-2/deficiência , Receptor PAR-2/genética , Receptor PAR-2/imunologia , Células Th2/imunologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Airway fibrosis is a prominent feature of asthma, contributing to the detrimental consequences of the disease. Fibrosis in the airway is the result of collagen deposition in the reticular lamina layer of the subepithelial tissue. Myofibroblasts are the leading cell type involved with this collagen deposition. Established methods of collagen deposition quantification present various issues, most importantly their inability to quantify current collagen biosynthesis occurring in airway myofibroblasts. Here, a novel method to quantify myofibroblast collagen expression in asthmatic lungs is described. Single cell suspensions of lungs harvested from C57BL/6 mice in a standard house dust mite model of asthma were employed to establish a flow cytometric method and compare collagen production in asthmatic and non-asthmatic lungs. Cells found to be CD45- αSMA+ , indicative of myofibroblasts, were gated, and median fluorescence intensity of the anti-collagen-I antibody labeling the cells was calculated. Lung myofibroblasts with no, medium, or high levels of collagen-I expression were distinguished. In asthmatic animals, collagen-I levels were increased in both medium and high expressers, and the number of myofibroblasts with high collagen-I content was elevated. Our findings determined that quantification of collagen-I deposition in myofibroblastic lung cells by flow cytometry is feasible in mouse models of asthma and indicative of increased collagen-I expression by asthmatic myofibroblasts. © 2018 International Society for Advancement of Cytometry.
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Asma/patologia , Pulmão/patologia , Fibrose Pulmonar/patologia , Animais , Asma/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fibroblastos/patologia , Citometria de Fluxo/métodos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The American Medical Society for Sports Medicine recognises a need to provide direction and continually enhance the quality of sports medicine fellowship training programmes. This document was developed to be an educational resource for sports medicine physicians who teach in a 1-year primary care sports medicine fellowship training programme. It is meant to provide high standards and targets for fellowship training programmes that choose to re-assess their curriculum and seek to make improvements.
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Bolsas de Estudo/normas , Medicina Esportiva/educação , Currículo/normas , Atenção Primária à Saúde , Sociedades Médicas , Estados UnidosRESUMO
The American Medical Society for Sports Medicine (AMSSM) recognizes a need to provide direction and continually enhance the quality of sports medicine fellowship training programs. This document was developed to be an educational resource for sports medicine physicians who teach in a 1-year primary care sports medicine fellowship training program. It is meant to provide high standards and targets for fellowship training programs that choose to reassess their curriculum and seek to make improvements.
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Currículo , Bolsas de Estudo/normas , Medicina Esportiva/educação , Competência Clínica , Docentes , Humanos , Sociedades MédicasRESUMO
Accumulating evidence shows a causative role for the bone marrow (BM) in the genesis and progression of pulmonary hypertension (PH). Engraftment of BM hematopoietic stem cells from PH patients to mice reproduces the cardiopulmonary pathology of PH. However, it is unknown whether healthy BM can prevent the development of right heart disease. Caveolin-1-deficient (CAV-1 KO) mice develop cardiopulmonary disease with manifestations resembling PH, including elevated right ventricular (RV) systolic pressure (RVSP), RV hypertrophy, and pulmonary endothelial proliferative disease. Here, we hypothesize that engraftment of healthy BM to CAV-1 KO mice will prevent pulmonary vascular remodeling and development of the cardiopulmonary disease. CAV-1 KO mice and wild-type (WT) mice underwent transplantation with WT or CAV-1 KO BM. Hematopoietic differentiation was analyzed by flow cytometry. Pulmonary endothelial remodeling was quantified by CD31 image analysis. RVSP and RV cardiomyocyte area or Fulton's index were used to analyze RV hypertrophy. Maladaptive RV hypertrophy was determined by quantification of RV fibrosis. Transplantation of CAV-1 KO BM into healthy recipient WT mice led to elevation of RVSP, RV hypertrophy, and pulmonary endothelial remodeling. Reconstitution of CAV-1 KO with WT BM prevented spontaneous development of PH, including elevation of RVSP and maladaptive RV hypertrophy, but not pulmonary endothelial remodeling. Healthy BM has a protective role in the right ventricle independent of pulmonary vascular disease.
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The number of girls participating in sports has increased significantly since the introduction of Title XI in 1972. As a result, more girls have been able to experience the social, educational, and health-related benefits of sports participation. However, there are risks associated with sports participation, including the female athlete triad. The triad was originally recognized as the interrelationship of amenorrhea, osteoporosis, and disordered eating, but our understanding has evolved to recognize that each of the components of the triad exists on a spectrum from optimal health to disease. The triad occurs when energy intake does not adequately compensate for exercise-related energy expenditure, leading to adverse effects on reproductive, bone, and cardiovascular health. Athletes can present with a single component or any combination of the components. The triad can have a more significant effect on the health of adolescent athletes than on adults because adolescence is a critical time for bone mass accumulation. This report outlines the current state of knowledge on the epidemiology, diagnosis, and treatment of the triad conditions.
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Síndrome da Tríade da Mulher Atleta , Adolescente , Osso e Ossos/fisiologia , Criança , Feminino , Síndrome da Tríade da Mulher Atleta/diagnóstico , Síndrome da Tríade da Mulher Atleta/epidemiologia , Síndrome da Tríade da Mulher Atleta/terapia , Humanos , Menstruação/fisiologia , Guias de Prática Clínica como AssuntoRESUMO
Children and adolescents who participate in intense sports training may face physical and psychologic stresses. The pediatric health care provider can play an important role in monitoring an athlete's preparation by obtaining a proper sports history, assessing sleep hygiene, discussing nutrition and hydration guidelines, and evaluating physiologic causes of fatigue. Educating parents and athletes on the potential risks of high-intensity training, inadequate rest and sleep, and a poor diet may improve the athlete's performance and prevent symptoms of overtraining syndrome. Infectious mononucleosis must also be considered a cause of fatigue among adolescents. The signs and symptoms of overtraining and burnout are discussed in this article.
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Desempenho Atlético , Fadiga/diagnóstico , Promoção da Saúde/métodos , Estresse Fisiológico , Estresse Psicológico/diagnóstico , Adolescente , Saúde do Adolescente , Atletas/psicologia , Desempenho Atlético/fisiologia , Desempenho Atlético/psicologia , Criança , Saúde da Criança , Fadiga/etiologia , Fadiga/prevenção & controle , Comportamentos Relacionados com a Saúde , Humanos , Pediatria , Esportes/fisiologia , Esportes/psicologia , Medicina Esportiva , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controleAssuntos
Transtornos Globais do Desenvolvimento Infantil/psicologia , Transtornos Globais do Desenvolvimento Infantil/reabilitação , Avaliação da Deficiência , Pais/psicologia , Adaptação Fisiológica , Adaptação Psicológica , Cuidadores/psicologia , Previsões , Humanos , Relações Interpessoais , Masculino , Narração , Reabilitação Vocacional , Medição de Risco , Transição para Assistência do AdultoRESUMO
Many women enjoy regular exercise as a part of a healthy lifestyle and may wish to continue exercising after they become pregnant. Some previously sedentary women may want to start an exercise program during pregnancy. Primary care and sports medicine physicians should understand the contraindications (eg, hypertension, diabetes, placenta previa, preeclampsia) and the concerns about exercise during pregnancy (eg, fetal nutrition, risk of preterm labor) and be able to offer reasonable guidelines to women who wish to start or continue exercise during pregnancy. Most non-weight-bearing exercises (eg, swimming, stationary bicycling) and walking are safe for pregnant women, beginning with 15 minutes of exercise three times a week and progressing as tolerated.
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Staying healthy is important at any stage of life, but especially while you are pregnant. You want to give your baby the best possible start by eating right, not smoking, getting enough rest, and exercising.