Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health ...consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.
The lifelong health of an individual is shaped during critical periods of development. The fetus is particularly susceptible to internal and external stimuli, many of which can alter developmental ...trajectories and subsequent susceptibility to disease. Glucocorticoids are critical in normal development of the fetus, as they are involved in the growth and maturation of many organ systems. The surge in fetal glucocorticoid levels that occurs in most mammalian species over the last few days of pregnancy is an important developmental switch leading to fundamental changes in gene regulation in many organs, including the brain. These changes are important for the transition to postnatal life. Exposure of the fetus to increased levels of glucocorticoids, resulting from maternal stress or treatment with synthetic glucocorticoids, can lead to long-term 'programming' of hypothalamic-pituitary-adrenal function and behaviours. Glucocorticoids act at multiple levels within the fetal brain. Growing evidence indicates that they can exert powerful effects on the epigenome, including on DNA methylation, histone acetylation and microRNA, to influence gene expression. Such influences probably represent a critical component of the 'programming' process, and might be partly responsible for the transgenerational effects of antenatal glucocorticoid exposure on neurologic, cardiovascular and metabolic function.
The early environment has a major impact on the developing embryo, fetus, and infant. Parental adversity (maternal and paternal) and glucocorticoid exposure before conception and during pregnancy ...have profound effects on the development and subsequent function of the hypothalamic-pituitary-adrenal axis and related behaviors. These effects are species-, sex-, and age-specific and depend on the timing and duration of exposure. The impact of these early exposures can extend across multiple generations, via both the maternal and paternal lineage, and recent studies have begun to determine the mechanisms by which this occurs. Improved knowledge of the mechanisms by which adversity and glucocorticoids program stress systems will allow development of strategies to ameliorate and/or reverse these long-term effects.
The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity ...and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival.
The evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity.
Collectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow.
•Glucocorticoid exposure in uteroaffects development through epigenetic mechanisms.•Excess glucocorticoid exposure in utero creates heritable changes in epigenome.•Inheritance occurs over multiple ...generations via maternal and paternal transmission.•Effects of excess glucocorticoid exposure in utero are sex-specific.
The embryo and fetus are highly responsive to the gestational environment. Glucocorticoids (GC) represent an important class of developmental cues and are crucial for normal brain development. Levels of GC in the fetal circulation are tightly regulated. They are maintained at low levels during pregnancy, and increase rapidly at the end of gestation. This surge in GC is critical for maturation of the organs, specifically the lungs, brain and kidney. There are extensive changes in brain epigenetic profiles that accompany the GC surge, suggesting that GC may drive regulation of gene transcription through altered epigenetic pathways. The epigenetic profiles produced by the GC surge can be prematurely induced as a result of maternal or fetal stress, as well as through exposure to synthetic glucocorticoids (sGC). This is highly clinically relevant as 10% of pregnant women are at risk for preterm labour and receive treatment with sGC to promote lung development in the fetus. Fetal overexposure to GC (including sGC) has been shown to cause lasting changes in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis leading to altered stress responses, and mood and anxiety disorders in humans and animals. In animal models, GC exposure is associated with transcriptomic and epigenomic changes that influence behaviour, HPA function and growth. Importantly, programming by GC results in sex-specific effects that can be inherited over multiple generations via paternal and maternal transmission.
Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific ...outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first‐generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long‐term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non‐coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long‐term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre‐clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.
Maternal obesity is an important risk factor for childhood obesity and influences the prevalence of metabolic diseases in offspring. As childhood obesity is influenced by postnatal factors, it is ...critical to determine whether children born to women with obesity during pregnancy show alterations that are detectable at birth. Epigenetic mechanisms such as DNA methylation modifications have been proposed to mediate prenatal programming. We investigated DNA methylation signatures in male and female infants from mothers with a normal Body Mass Index (BMI 18.5-24.9 kg/m2) compared to mothers with obesity (BMI≥30 kg/m2). BMI was measured during the first prenatal visit from women recruited into the Ontario Birth Study (OBS) at Mount Sinai Hospital in Toronto, ON, Canada. DNA was extracted from neonatal dried blood spots collected from heel pricks obtained 24 hours after birth at term (total n = 40) from women with a normal BMI and women with obesity matched for parity, age, and neonatal sex. Reduced representation bisulfite sequencing was used to identify genomic loci associated with differentially methylated regions (DMRs) in CpG-dense regions most likely to influence gene regulation. DMRs were predominantly localized to intergenic regions and gene bodies, with only 9% of DMRs localized to promoter regions. Genes associated with DMRs were compared to those from a large publicly available cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC; total n = 859). Hypergeometric tests revealed a significant overlap in genes associated with DMRs in the OBS and ALSPAC cohorts. PTPRN2, a gene involved in insulin secretion, and MAD1L1, which plays a role in the cell cycle and tumor suppression, contained DMRs in males and females in both cohorts. In males, KEGG pathway analysis revealed significant overrepresentation of genes involved in endocytosis and pathways in cancer, including IGF1R, which was previously shown to respond to diet-induced metabolic stress in animal models and in lymphocytes in the context of childhood obesity. These preliminary findings are consistent with Developmental Origins of Health and Disease paradigm, which posits that adverse prenatal exposures set developmental health trajectories.
•Recent developments in automatically detecting compromised pig health and welfare.•Five categories of behaviour are reviewed.•Behaviours mapped to sensors that are feasible for automated ...detection.•Progress towards levels of automation through detection, monitoring and fully automatic detection of behavioural change.•Challenges for automated detection of behavioural changes are multifaceted and require trade-offs to develop such systems.
Early detection of health and welfare compromises in commercial piggeries is essential for timely intervention to enhance treatment success, reduce impact on welfare, and promote sustainable pig production. Behavioural changes that precede or accompany subclinical and clinical signs may have diagnostic value. Often referred to as sickness behaviour, this encompasses changes in feeding, drinking, and elimination behaviours, social behaviours, and locomotion and posture. Such subtle changes in behaviour are not easy to quantify and require lengthy observation input by staff, which is impractical on a commercial scale. Automated early-warning systems may provide an alternative by objectively measuring behaviour with sensors to automatically monitor and detect behavioural changes. This paper aims to: (1) review the quantifiable changes in behaviours with potential diagnostic value; (2) subsequently identify available sensors for measuring behaviours; and (3) describe the progress towards automating monitoring and detection, which may allow such behavioural changes to be captured, measured, and interpreted and thus lead to automation in commercial, housed piggeries. Multiple sensor modalities are available for automatic measurement and monitoring of behaviour, which require humans to actively identify behavioural changes. This has been demonstrated for the detection of small deviations in diurnal drinking, deviations in feeding behaviour, monitoring coughs and vocalisation, and monitoring thermal comfort, but not social behaviour. However, current progress is in the early stages of developing fully automated detection systems that do not require humans to identify behavioural changes; e.g., through automated alerts sent to mobile phones. Challenges for achieving automation are multifaceted and trade-offs are considered between health, welfare, and costs, between analysis of individuals and groups, and between generic and compromise-specific behaviours.
Since animals express their internal state through behaviour, changes in said behaviour may be used to detect early signs of problems, such as in animal health. Continuous observation of livestock by ...farm staff is impractical in a commercial setting to the degree required to detect behavioural changes relevant for early intervention. An automated monitoring system is developed; it automatically tracks pig movement with depth video cameras, and automatically measures standing, feeding, drinking, and locomotor activities from 3D trajectories. Predictions of standing, feeding, and drinking were validated, but not locomotor activities. An artificial, disruptive challenge; i.e., introduction of a novel object, is used to cause reproducible behavioural changes to enable development of a system to detect the changes automatically. Validation of the automated monitoring system with the controlled challenge study provides a reproducible framework for further development of robust early warning systems for pigs. The automated system is practical in commercial settings because it provides continuous monitoring of multiple behaviours, with metrics of behaviours that may be considered more intuitive and have diagnostic validity. The method has the potential to transform how livestock are monitored, directly impact their health and welfare, and address issues in livestock farming, such as antimicrobial use.
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