Developmental Origins Of Health And Disease Research Articles

The roles of the gut microbiota, metabolites, and epigenetics in the effects of maternal exercise on offspring metabolism.

Metabolic diseases, including obesity, dyslipidemia, and type 2 diabetes, have become severe challenges worldwide. The developmental origins of health and disease (DOHaD) hypothesis suggests that an adverse intrauterine environment can increase the risk of metabolic disorders in offspring. Studies have demonstrated that maternal exercise is an effective intervention for improving the offspring metabolic health. However, the pathways through which exercise works are unclear. It has been reported that the gut microbiota mediates the effect of maternal exercise on offspring metabolism, and epigenetic modifications have also been proposed to be important molecular mechanisms. Microbial metabolites can influence epigenetics by providing substrates for DNA or histone modifications, binding to G-protein coupled receptors to affect downstream pathways, or regulating the activity of epigenetic modifying enzymes. This review aims to summarize the intergenerational effect of maternal exercise and proposes that gut microbiota-metabolites-epigenetic regulation is an important mechanism by which maternal exercise improves offspring metabolism, which may yield novel targets for the early prevention and intervention of metabolic diseases.

Timing determines programming of energy homeostasis by maternal PM2.5 exposure in mouse models

Maternal exposure to particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) is believed to be a risk factor of developmental origins of health and disease (DOHaD), but its effect on offspring's susceptibility to obesity, a common target disease of DOHaD, remains controversial. To pinpoint the effect of maternal PM2.5 exposure on offspring's energy homeostasis, female C57BL/6J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 12 weeks and mated with normal male mice to produce offspring. After parturition, a cross-fostering strategy was exploited to determine whether prenatal and/or postnatal mothering by CAP-exposed dams program offspring's energy homeostasis and susceptibility to obesity. Moreover, oocytes were collected from FA- or CAP-exposed mice and subjected to in vitro fertilization (IVF) to determine whether maternal pre-conceptional exposure to PM2.5 programs energy homeostasis. Results showed that prenatal mothering by CAP-exposed dams increased suckling's milk intake and weight gain, decreased normal diet (ND)-fed offspring's adulthood food intake and body weight, and did not influence offspring's diet-induced obesity (DIO). Postnatal mothering by CAP-exposed dams did not influence suckling's milk intake and weight gain, increased ND-fed offspring's adulthood food intake and body weight and did not influence offspring's DIO. Prenatal plus postnatal mothering by CAP-exposed dams increased suckling's milk intake and weight gain, increased ND-fed offspring's adulthood food intake and body weight, and aggravated offspring's DIO. IVF study revealed that male offspring derived from CAP-exposed mice versus controls had significantly decreased adulthood food intake and body weight. RNA sequencing showed that CAP exposure influenced oocyte estrogen signaling and histone methylation. This study thus clearly reveals that timing determines programming of energy homeostasis by maternal PM2.5 exposure.

Epigenetic programming of obesity in early life through modulation of the kynurenine pathway.

Childhood obesity is a global health concern that has its origins before birth. Although genetics plays a crucial role, increasing evidence suggests that epigenetic modifications during fetal life could also influence its incidence. In this model, during the fetal period, interactions between genetic makeup, intrauterine factors, and environmental conditions, increase the risk of childhood obesity. This is in accordance with the Developmental Origins of Health and Disease (DOHaD) hypothesis, in which specific intrauterine environments can have long-lasting effects on the immune system's essential functions during crucial stages of fetal growth, resulting in permanent changes to the immune function of the offspring. Consequently, dysfunction can consequently make the offspring more prone to inflammatory and immune-related disorders later in life. In this review, we examine how maternal inflammation could influence the risk of childhood obesity. We propose that during pregnancy, modification of the expression of critical genes in metabolic and signaling pathways, such as the kynurenine (Kyn) pathway, occurs due to increased levels of maternal inflammation. We also propose that such expression differences are mediated by epigenetic changes. Furthermore, we also hypothesize that the Kyn pathway produces metabolites that have immunoregulatory effects and may play a crucial role in regulating inflammation during pregnancy. As a result, interventions aimed at improving maternal inflammation may be able to help alleviate the risk of childhood obesity.

Knowledge, attitudes, and practices of paediatric medical officers and registrars on the developmental origins of health and disease in a tertiary women’s and children’s hospital

BackgroundTo mitigate the growing burden of non-communicable diseases, doctors training to become paediatricians should be equipped with concepts and knowledge regarding Developmental Origins of Health and Disease (DOHaD).MethodsWe assessed the knowledge, attitudes, and practices (KAP) of medical officers, resident physicians, as well as junior and senior residents practising in the paediatric department of a tertiary women’s and children’s hospital. This was done through a cross-sectional online survey, with questions developed after focused group discussions with domain experts, and responses based on a 5-point Likert scale.ResultsA total of 95 physicians met the inclusion criteria, grouped into Medical Officers (MOs) and Registrars (REGs), and we received a 100% response rate. Results showed that few physicians (n = 22, 23.2%) knew the term DOHaD, and majority rated their colleagues to be inadequately informed (n = 84, 88.4%). Among the physicians, one third (n = 32, 33.7%) were not confident in their ability to counsel patients about initiating healthy feeding practices to prevent future metabolic diseases in their children. However, there was a readiness to be better equipped with DOHaD principles and knowledge, and 95.8% (n = 91) strongly acknowledged the physician’s responsibility to optimise early life determinants of cardiometabolic health.ConclusionIn conclusion, the findings suggest a poor translation of DOHaD concepts, indicating that bridging the gap between DOHaD research knowledge and clinical application represents an unmet need. These principles should be inculcated early in the professional training of all healthcare providers.

Advocacy for DOHaD research optimizing child kidney health

Emerging antenatal risk factors have been associated with an increased risk of kidney disease throughout the offspring's life course. However, the intricate kidney programming mechanisms underlying these risks remain complex and are incompletely understood, but they are rooted in structural and functional alterations within the kidneys. The Developmental Origins of Health and Disease (DOHaD) theory underscores the significance of elucidating core mechanisms initiated through the maternal-fetal interface, which trigger kidney programming. Furthermore, it offers a promising avenue for preventing kidney disease at its earliest stages through a process known as reprogramming. This concise review aims to synthesize existing knowledge regarding the impact of kidney programming on offspring kidney disease and to provide an overview of documented reprogramming strategies as observed in animal models of kidney programming. By consolidating this information, we aim to expedite the translation of research breakthroughs into practical clinical solutions, ultimately resulting in enhanced outcomes for children facing kidney-related issues.

Non-communicable diseases: Opportunities to promote future health during the first 1000 day of life

The Developmental Origins of Health and Disease (DOHaD) framework now underlies the evolution and epigenetics of many non-communicable diseases that develop in adult life. Type 2 diabetes, obesity, hypertension, heart disease and stroke in particular have links back to events during the first 1000 days of life, and as the world is witnessing an epidemic of these conditions, identifying measures able to contribute to reducing the potential for these NCDs to develop in our aging populations becomes all the more important. Parental health at conception and good maternal health and nutrition throughout pregnancy are known to be integral to normal infant development and health in later life, but more recently the central importance of infant nutrition that achieves healthy weight gain has become recognized. In this context, achieving growth patterns for infants that avoid either the onset of obesity or development of stunting during the first 1000 days of life appears to be an achievable goal with significant potential for the avoidance of many NCDs in later life. Hence the relevance of health promotion initiatives to share this knowledge among health care providers and educate parents on the benefits of optimal infant nutrition.

Mandible development under gestational protein restriction: cellular and molecular mechanisms.

Insufficient evidence regarding how maternal undernutrition affects craniofacial bone development persists. With its unique focus on the impact of gestational protein restriction on calvaria and mandible osteogenesis, this study aims to fill, at least in part, this gap. Female mice were mated and randomized into NP (normal protein) or LP (low protein) groups. On the 18th gestational day (GD), male embryos were collected and submitted to microtomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), PCR, and autophagy dynamic analyses. The study shows that the LP offspring exhibited lower body mass than the NP group, with µCT analysis revealing no volumetric differences in fetus's head. EDS analysis showed lower calcium and higher phosphorus percentages in mandibles and calvaria. SEM assessment evidenced higher hydroxyapatite crystal-like (HC) deposition on the calvaria surface in LP fetus. Conversely, lower HC deposition was observed on the mandible surface, suggesting delayed matrix mineralization in LP fetuses with a higher percentage of collagen fibers in the mandible bone. The autophagy process was reduced in the mesenchyme of LP fetuses. PCR array analysis of 84 genes revealed 27 genes with differential expression in the LP progeny-moreover, increased mRNA levels of Akt1, Mtor, Nfkb, and Smad1 in the LP offspring. In conclusion, the results suggest that gestational protein restriction anticipated bone differentiation in utero, before 18GD, where this process is reduced compared to the control, leading to the reduction in bone area at 15 postnatal day previously observed. These findings provide insights into the molecular and cellular mechanisms of mandible development and suggest potential implications for the Developmental Origins of Health and Disease (DOHaD).

Developmental neurotoxicity of PFOA exposure on hiPSC-derived cortical neurons

PFOA is a legacy Per- and Polyfluorinated Substances (PFAS), a group of chemicals widely used in various industrial applications and consumer products. Although there has been a voluntary phase out of PFOA since 2005, it is still widely detected in various water supplies. A growing body of evidence suggests an association between PFOA exposure, particularly during developmental stages, with increased risks of neurodegenerative diseases (NDs). The neurotoxic mechanism of developmental PFOA exposure, however, remains poorly understood. Utilizing human induced-pluripotent stem cell (hiPSC)-derived cortical neurons, we investigated the effect of PFOA exposure prior to differentiation and assessed changes in neuronal characteristics, transcriptome, and neurodegeneration markers mimicking a Developmental Origin of Health and Disease (DoHAD) paradigm. Exposure to PFOA before neuron differentiation resulted in persistent alterations in nuclear morphology, neuronal network, and calcium activity. RNA sequencing analysis further revealed transcriptomic changes aligning with Alzheimer’s Disease (AD) after PFOA exposure. These observations were further corroborated by alterations in tau phosphorylation markers, the presence of fibrillar tau, an increase in liquid droplets, and a decrease in RNA translational efficiency characterized using a battery of biochemical assays. Taken together, our results revealed persistent deficits of key neuronal characteristics induced by pre-differentiation PFOA exposure, suggesting impairments in several AD-related pathways that can together contribute to the elevation of AD risk after pre-differentiation PFOA exposure.

Adolescent understanding of concepts related to the developmental origins of health and disease: a Pacific perspective

ABSTRACT The Developmental Origins of Health and Disease (DOHaD) framework has highlighted the link between an adverse early life environment and later disease risk. There is an increasing focus on adolescents as the next generation of parents as DOHaD agents of change to break the disease cycle. However, DOHaD awareness in adolescents is key to enabling knowledge uptake and behavioural change, particularly in Pacific adolescents who have a higher non-communicable disease (NCD) burden. The present study investigated understanding of DOHaD-related concepts among Pacific, Māori and other ethnic groups in New Zealand (ages 16–19 years, n = 209). Awareness of the term NCDs was low across all groups with awareness of the term DOHaD or the First 1000 Days lower in the Pacific group compared to others. Similarly, awareness of some key DOHaD concepts was low overall with some gender differences in response within ethnicity. Interestingly, adolescents' understanding that the early life nutritional environment can impact health across the life-course diminishes significantly with each advancing life-course stage. These results indicate that both education and healthcare DOHaD-related health promotion are lacking with a need for increased engagement with adolescents, particularly Pacific adolescents, to develop and communicate DOHaD content and messaging relevant to this demographic.

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.

Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.

No relationship found between dental fluctuating asymmetry, birthweight, and birth term in two modern North American samples.

Deciduous dental crowns primarily develop during gestation and early infancy and embody early life stress exposures. Composite measures of dental fluctuating asymmetry (DFA) generated from the deciduous teeth may therefore indicate cumulative gestational stress in developmental origins of health and disease (DOHaD) studies. This study examines whether higher composite measures of deciduous DFA are associated with low birthweight and prematurity, two aspects of birth phenotype consistently associated with increased morbidity and mortality risks in adulthood. We evaluated associations between composite deciduous DFA, birthweight, and birth term in two contemporary North American samples: an autopsy sample from New Mexico (n = 94), and sample from a growth cohort study in Burlington, Ontario (n = 304). Dental metric data for each sample was collected from postmortem CT scans and dental casts, respectively. Composite DFA was estimated using buccolingual (BL) and mesiodistal (MD) crown diameters from paired deciduous teeth. Contrary to expectations, the results of linear regression indicated no significant relationship between birthweight and DFA, or birth term and DFA, in either sample. Deciduous DFA does not predict aspects of birth phenotype associated with gestational stress. Birthweight and birth term are plastic relative to the more developmentally stable deciduous dentition, which may only subtly embody early life stress. We suggest that deciduous DFA should be utilized with caution in DOHaD studies until its relationship with gestational stress is clarified.

Contribution of the seminal microbiome to paternal programming.

The field of Developmental Origins of Health and Disease has primarily focused on maternal programming of offspring health. However, emerging evidence suggests that paternal factors, including the seminal microbiome, could potentially play important roles in shaping the developmental trajectory and long-term offspring health outcomes. Historically, the microbes present in the semen were regarded as inherently pathogenic agents. However, this dogma has recently been challenged by the discovery of a diverse commensal microbial community within the semen of healthy males. In addition, recent studies suggest that the transmission of semen-associated microbes into the female reproductive tract during mating has potentials to not only influence female fertility and embryo development but could also contribute to paternal programming in the offspring. In this review, we summarize the current knowledge on the seminal microbiota in both humans and animals followed by discussing their potential involvement in paternal programming of offspring health. We also propose and discuss potential mechanisms through which paternal influences are transmitted to offspring via the seminal microbiome. Overall, this review provides insights into the seminal microbiome-based paternal programing, which will expand our understanding of the potential paternal programming mechanisms which are currently focused primarily on the epigenetic modifications, oxidative stresses, and cytokines.

Early-life exposures and long-term health: adverse gestational environments and the programming of offspring renal and vascular disease.

According to the Developmental Origins of Health and Disease hypothesis, exposure to certain environmental influences during early life may be a key determinant of fetal development and short- and long-term offspring health. Indeed, adverse conditions encountered during the fetal, perinatal, and early childhood stages can alter normal development and growth, as well as put the offspring at elevated risk of developing long-term health conditions in adulthood, including chronic kidney disease and cardiovascular diseases. Of relevance in understanding the mechanistic basis of these long-term health conditions are previous findings showing low glomerular number in human intrauterine growth restriction and low birth weight-indicators of a suboptimal intrauterine environment. In different animal models, the main suboptimal intrauterine conditions studied relate to maternal dietary manipulations, poor micronutrient intake, prenatal ethanol exposure, maternal diabetes, glucocorticoid and chemical exposure, hypoxia, and placental insufficiency. These studies have demonstrated changes in kidney structure, glomerular endowment, and expression of key genes and signaling pathways controlling endocrine, excretion, and filtration function of the offspring. This review aims to summarize those studies to uncover the effects and mechanisms by which adverse gestational environments impact offspring renal and vascular health in adulthood. This is important for identifying agents and interventions that can prevent and mitigate the long-term consequences of an adverse intrauterine environment on the subsequent generation.NEW & NOTEWORTHY Human data and experimental animal data show that suboptimal environments during fetal development increase the risk of renal and vascular diseases in adult-life. This is related to permanent changes in kidney structure, function, and expression of genes and signaling pathways controlling filtration, excretion, and endocrine function. Uncovering the mechanisms by which offspring renal development and function is impacted is important for identifying ways to mitigate the development of diseases that strain health care services worldwide.

Amino Acids during Pregnancy and Offspring Cardiovascular-Kidney-Metabolic Health.

Amino acids are essential for normal pregnancy and fetal development. Disruptions in maternal amino acid metabolism have been associated with various adult diseases later in life, a phenomenon referred to as the developmental origins of health and disease (DOHaD). In this review, we examine the recent evidence highlighting the significant impact of amino acids on fetal programming, their influence on the modulation of gut microbiota, and their repercussions on offspring outcomes, particularly in the context of cardiovascular-kidney-metabolic (CKM) syndrome. Furthermore, we delve into experimental studies that have unveiled the protective effects of therapies targeting amino acids. These interventions have demonstrated the potential to reprogram traits associated with CKM in offspring. The discussion encompasses the challenges of translating the findings from animal studies to clinical applications, emphasizing the complexity of this process. Additionally, we propose potential solutions to overcome these challenges. Ultimately, as we move forward, future research endeavors should aim to pinpoint the most effective amino-acid-targeted therapies, determining the optimal dosage and mode of administration. This exploration is essential for maximizing the reprogramming effects, ultimately contributing to the enhancement of cardiovascular-kidney-metabolic health in offspring.

Influence of Environmental Factors on Embryonic Development and Fetal Programming in South Africa

Purpose: The aim of the study was to investigate the influence of environmental factors on embryonic development and fetal programming Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study revealed compelling evidence linking various environmental exposures, including air pollution, maternal nutrition, smoking, stress, chemical contaminants, and heavy metals, to adverse pregnancy outcomes and long-term health consequences for offspring. The study also highlighted the critical role of epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, in mediating the effects of environmental factors on gene expression and cellular function during embryogenesis. Unique Contribution to Theory, Practice and Policy: Developmental Origins of Health and Disease (DOHaD) theory & Fetal Programming theory may be used to anchor future studies on the influence of environmental factors on embryonic development and fetal programming. Incorporate comprehensive assessments of environmental exposures into routine prenatal care. Healthcare providers should consider factors such as maternal diet, smoking status, stress levels, chemical exposures, and air quality when counseling pregnant individuals. Advocate for stricter environmental regulations aimed at reducing exposure to air pollutants, endocrine-disrupting chemicals, heavy metals, and other harmful substances during pregnancy. Tailor interventions based on individual risk profiles and environmental exposures. For example, provide targeted nutritional counseling, smoking cessation programs, stress management support, and referrals for environmental health assessments as part of prenatal care services.

The effect of low birth weight as an intrauterine exposure on the early onset of sarcopenia through possible molecular pathways.

Sarcopenia, a musculoskeletal disease characterized by the progressive loss of skeletal muscle mass, strength, and physical performance, presents significant challenges to global public health due to its adverse effects on mobility, morbidity, mortality, and healthcare costs. This comprehensive review explores the intricate connections between sarcopenia and low birth weight (LBW), emphasizing the developmental origins of health and disease (DOHaD) hypothesis, inflammatory processes (inflammaging), mitochondrial dysfunction, circadian rhythm disruptions, epigenetic mechanisms, and genetic variations revealed through genome-wide studies (GWAS). A systematic search strategy was developed using PubMed to identify relevant English-language publications on sarcopenia, LBW, DOHaD, inflammaging, mitochondrial dysfunction, circadian disruption, epigenetic mechanisms, and GWAS. The publications consist of 46.2% reviews, 21.2% cohort studies, 4.8% systematic reviews, 1.9% cross-sectional studies, 13.4% animal studies, 4.8% genome-wide studies, 5.8% epigenome-wide studies, and 1.9% book chapters. The review identified key factors contributing to sarcopenia development, including the DOHaD hypothesis, LBW impact on muscle mass, inflammaging, mitochondrial dysfunction, the influence of clock genes, the role of epigenetic mechanisms, and genetic variations revealed through GWAS. The DOHaD theory suggests that LBW induces epigenetic alterations during foetal development, impacting long-term health outcomes, including the early onset of sarcopenia. LBW correlates with reduced muscle mass, grip strength, and lean body mass in adulthood, increasing the risk of sarcopenia. Chronic inflammation (inflammaging) and mitochondrial dysfunction contribute to sarcopenia, with LBW linked to increased oxidative stress and dysfunction. Disrupted circadian rhythms, regulated by genes such as BMAL1 and CLOCK, are associated with both LBW and sarcopenia, impacting lipid metabolism, muscle mass, and the ageing process. Early-life exposures, including LBW, induce epigenetic modifications like DNA methylation (DNAm) and histone changes, playing a pivotal role in sarcopenia development. Genome-wide studies have identified candidate genes and variants associated with lean body mass, muscle weakness, and sarcopenia, providing insights into genetic factors contributing to the disorder. LBW emerges as a potential early predictor of sarcopenia development, reflecting the impact of intrauterine exposures on long-term health outcomes. Understanding the complex interplay between LBW with inflammaging, mitochondrial dysfunction, circadian disruption, and epigenetic factors is essential for elucidating the pathogenesis of sarcopenia and developing targeted interventions. Future research on GWAS and the underlying mechanisms of LBW-associated sarcopenia is warranted to inform preventive strategies and improve public health outcomes.

Prenatal influences on postnatal neuroplasticity: Integrating DOHaD and sensitive/critical period frameworks to understand biological embedding in early development.

Early environments can have significant and lasting effects on brain, body, and behavior across the lifecourse. Here, we address current research efforts to understand how experiences impact neurodevelopment with a new perspective integrating two well-known conceptual frameworks - the Developmental Origins of Health and Disease (DOHaD) and sensitive/critical period frameworks. Specifically, we consider how prenatal experiences characterized in the DOHaD model impact two key neurobiological mechanisms of sensitive/critical periods for adapting to and learning from the postnatal environment. We draw from both animal and human research to summarize the current state of knowledge on how particular prenatal substance exposures (psychoactive substances and heavy metals) and nutritional profiles (protein-energy malnutrition and iron deficiency) each differentially impact brain circuits' excitation/GABAergic inhibition balance and myelination. Finally, we highlight new research directions that emerge from this integrated framework, including testing how prenatal environments alter sensitive/critical period timing and learning and identifying potential promotional/buffering prenatal exposures to impact postnatal sensitive/critical periods. We hope this integrative framework considering prenatal influences on postnatal neuroplasticity will stimulate new research to understand how early environments have lasting consequences on our brains, behavior, and health.

Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals- a pragmatic serial cross-sectional study.

The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal.

Quantification of the effect of in utero events on lifetime resilience in dairy cows

Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, as well as good reproductive performance and milk yield. There is much evidence that events in utero, that is, the developmental origins of health and disease hypothesis, alter the life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system, based on longevity with secondary corrections for age at first calving and calving interval, and to quantify the effects of in utero events on the LRS using 2 datasets. The first was a large dataset of cattle on 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular dataset of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the effect of heat stress as measured by temperature-humidity index, and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring; however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams that recorded a high maximum locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS, and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS. Although "big data" can contain a considerable amount of noise, similar findings between the 2 datasets indicate it is likely these findings are real.

Microplastics exposure: implications for human fertility, pregnancy and child health.

Plastics found in our everyday environment are becoming an increasing concern for individual and population-level health, and the extent of exposure and potential toxic effects of these contaminants on numerous human organ systems are becoming clear. Microplastics (MPs), tiny plastic particles, appear to have many of the same biological effects as their plastic precursors and have the compounded effect of potential accumulation in different organs. Recently, microplastic accumulation was observed in the human placenta, raising important questions related to the biological effects of these contaminants on the health of pregnancies and offspring. These concerns are particularly heightened considering the developmental origins of health and disease (DOHaD) framework, which postulates that in utero exposure can programme the lifelong health of the offspring. The current review examines the state of knowledge on this topic and highlights important avenues for future investigation.