The prenatal period, childhood, and adolescence are critical periods of development characterized by high plasticity. As an extension of the Developmental Origins of Health and Disease (DOHaD) paradigm, known as Origins of Paternal Health and Disease (POHaD), recent studies in rodents provide evidence that paternal obesity is associated not only with infertility but also with an increased risk of metabolic disorders in the offspring. In rodents, litter size reduction is used to induce lactational overfeeding by increasing the amount of breast milk to pups, which causes metabolic and reproductive disorders in adulthood. This work evaluated the metabolic and reproductive alterations in the offspring of males raised in normal or small litter (SL) in the prepubertal period and in adult life. The results show that paternal obesity due to early overfeeding affects the offspring in a sex-specific manner. During the prepubertal period, male offspring of SL fathers showed decreased Lee index, tibia length, and HDL plasma levels, and increased weight of gastrocnemius muscle, while female offspring of SL fathers only showed reduced HDL plasma levels. In adulthood, male offspring of overfed males showed glucose intolerance and reduced food intake and triglycerides plasma levels, signs of metabolic dysfunction. Female offspring of overfed males showed delayed puberty onset and higher prevalence of infertile periods in the estrous cycles, indicating a potential susceptibility to reproductive dysfunction. The results of the current study show that paternal obesity due to early overfeeding affects energy balance and reproduction of their offspring in a sex-specific manner.
Maternal malnutrition affects millions of people worldwide in two main ways: through food insecurity and hunger, as well as through diets high in ultra-processed, low-nutrient foods. These effects are often linked to deficiencies in specific macronutrients and micronutrients, which can lead to organ-specific consequences in the biological development of the child-a context explored within the framework of the Developmental Origins of Health and Disease (DOHaD). Given the extensive effects of maternal protein restriction (MPR) on offspring development, this review focuses specifically on low-protein diets and their impact on various organs and systems. It compiles both experimental and epidemiological data across different developmental stages. Poor maternal nutrition can impair embryonic and fetal development, creating a stressful microenvironment for both mother and child from the earliest stages of life. This stress can leave epigenetic marks that influence health and disease outcomes later in life. Numerous studies have documented the wide-ranging consequences of malnutrition, highlighting its detrimental effects on metabolic, molecular, and phenotypic systems. This narrative review aims to present both the immediate and long-term effects of exposure to MPR throughout the lifespan of the offspring.
Tryptophan, an essential amino acid in mammals that is obtained from the diet, has impacts on early life and development. This amino acid is being studied under the Developmental Origins of Health and Disease (DOHaD) concept, which has led to findings of factors from conception to early childhood that affect health and susceptibility to disease. Tryptophan is metabolized mainly through 2 pathways, serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system. Serotonin also regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include trp-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO) in the kynurenine pathway and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2) in the serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, which is rich in tryptophan and protective bioactive molecules. Tryptophan, derived solely from breast milk, is crucial for infants. Its levels are high in newborns, 2-4 times higher than in adults during the first 3 weeks postpartum, and then gradually declining to adult levels by the fourth week. Due to the remarkable role of tryptophan in organic development, disturbances in tryptophan metabolism at different life stages, fetal or postnatal, may lead to modifications of its metabolism related to pathological states in adult life. We bring some of this evidence to this review.
Environmental exposure to micro- and nanoplastics (MNPs) can have significant impacts on the development of chronic health conditions in children and adults. MNPs are byproducts generated from the ubiquitous and daily use of plastics. A growing body of literature points to MNPs' affecting human metabolic and reproductive health, yet research into their potential impacts is still in its infancy. Due to recent evidence demonstrating accumulation of MNPs within human metabolic and reproductive tissues, their potential for inducing physiological and epigenetic dysregulations is postulated. This is especially critical for future generations as epigenetic disturbances within individuals can be inherited. Currently, the mechanisms for how MNPs exert their effects are still under investigation. In this scenario, the developmental origins of health and disease (DOHaD) offers insight on the influence of environmental exposures in the periconceptual, fetal, and early phases of life towards the development of noncommunicable diseases later in life. DOHaD investigates these interactions through an epigenetic lens as epigenetics bridges environmental exposures and changes in gene expression outside of the DNA sequence itself. In this review, we provide an overview on current research that describes MNPs' contribution towards the development of metabolic and reproductive dysfunction as well as their potential to impact future generations through the DOHaD paradigm possibly mediated by epigenetic modifications.
Developmental programming has emerged as one of the major biological principles and biomedical issues of this century because of its potential for long-term, even transgenerational, effects on the health and productivity of offspring. Livestock models have been widely used to establish the mechanisms of developmental programming in fetuses and offspring, and accordingly present data with dual benefits; both serving animal agricultural purposes and providing insights for biomedical applications. Livestock models have furthered our understanding of how developmental processes can influence postnatal health and productivity in the short- and long-term. In addition, because livestock are key to agricultural sustainability and food security, studies in livestock contribute to human livelihood. In this review, we will focus on the influence of maternal nutrition in livestock models on developmental outcomes. Maternal nutritional models include global nutrient intake (over- and under-nutrition) and supplementation of specific macro and micronutrients. Specifically, we will review the effects of maternal nutrition on: placental function, key metabolic tissues of the fetus/offspring (visceral tissues, skeletal muscle, and immune system), genetics, epigenetics, and transgenerational programming, parturition, and the underlying mechanism of developmental programming. Lastly, we will focus on gaps in knowledge and future research directions.
The Developmental Origins of Health and Disease (DOHaD) paradigm posits that early environmental factors may influence a child’s development and long-term health outcomes. Developmental programming (DP) is central to this paradigm, whereby specific early life exposures during critical periods of development are associated with changes to physiological and metabolic pathways, potentially predisposing individuals to disease. However, no standard definition of DP exists, and various terms have been used to describe similar processes. This analysis aimed to develop a conceptual definition for DP to inform interdisciplinary research, education, and practice. Walker and Avant’s eight-step method was employed to analyze the literature, incorporating elements of Rogers’ evolutionary approach to present the temporal and contextual evolution of the concept. A systematic search of MEDLINE with the EBSCOhost database was performed using the search term “developmental programming,” resulting in 95 titles included in this review. Defining attributes associated with DP include epigenetics, ontogeny, critical periods, and plasticity. Antecedents for DP may include maternal and infant nutrition, maternal disease and medication, lifestyle choices, environmental exposures, and stress. The potential consequences include cardiovascular disease, metabolic disorders, diabetes, neurodevelopmental disorders, endocrine disruption, reproductive issues, and mental health conditions. Effective healthcare provider education, knowledge dissemination, and addressing the social determinants of health through a population health approach are essential to translate DP theory and empirical evidence into practice. A common language and understanding of DP can improve the interdisciplinary advancement of DOHaD research to inform practice and education.
The fetus and neonate are especially vulnerable to toxic effects of polychlorinated biphenyls (PCBs), that have been shown to perturb behavioral and neuropsychological development. This study aimed to examine the long-term effects of developmental exposure to PCBs. Doses selected were environmentally relevant to those found in epidemiological studies, on the central nervous system (CNS) of adult rat offspring. Pregnant Sprague Dawley rats were fed cookies that contained a mixture of fourteen PCBs or vehicle (corn oil) daily. PCB doses were 0.011 mg/kg maternal body weight/day ("low") or 1.10 mg/kg maternal body weight/day ("high"), for 42 days throughout gestation and lactation. Adult offspring were euthanized on postnatal day 450. A battery of immunohistochemical markers of brain structure and function were selected to assess possible effects of developmental PCB exposure. Using a 3×2 factorial design (treatment and sex), two-way analysis of variance revealed significant effects of treatment through the CNS, with no main effect of sex or interaction effects. In comparison with controls, both low and high dose developmental PCB exposure significantly (p < 0.05) increased inhibitory enzyme glutamic acid decarboxylase (GAD67) immunoreactivity in the cerebellar vermis, and decreased lipofuscin autofluorescence in the locus coeruleus (LC). Low dose developmental PCB exposure significantly decreased the perimeter of endothelial cells in the periaqueductal gray, ventral orbitofrontal cortex; and decreased lipofuscin in the dorsal striatum, compared to controls. Findings support the Developmental Origins of Health and Disease concept, which broadly posits that early-life perturbations may influence health trajectories over the lifespan.
A molecular understanding of lung organogenesis requires delineation of the timing and regulation of the cellular transitions that ultimately form and support a surface capable of gas exchange. Although the advent of single-cell transcriptomics has allowed for the discovery and identification of transcriptionally distinct cell populations present during lung development, the spatiotemporal dynamics of these transcriptional shifts remain undefined. With imaging-based spatial transcriptomics, we analyzed the gene expression patterns in 17 human infant lungs at varying stages of development and injury, creating a spatial transcriptomic atlas of approximately 1.2 million cells. We applied computational clustering approaches to identify shared molecular patterns among this cohort, informing how tissue architecture and molecular spatial relationships are coordinated during development and disrupted in disease. Recognizing that all preterm birth represents an injury to the developing lung, we created a simplified classification scheme that relies upon the routinely collected objective measures of gestational age and lifespan. Within this framework, we have identified cell type patterns across gestational age and life span variables that would likely be overlooked when using the conventional "disease versus control" binary comparison. Together, these data represent an open resource for the lung research community, supporting discovery-based inquiry and identification of targetable molecular mechanisms in both normal and arrested human lung development.NEW & NOTEWORTHY Mapping the spatial and temporal transcriptional relationships during lung development is fundamental to understanding regeneration and chronic lung disease; however, the classification of samples as control or disease is especially challenging in the setting of preterm birth (itself a lung injury). Here, we report the largest neonatal lung transcriptomic atlas to date and an analysis framework based only on gestational age and lifespan, providing a new resource for hypothesis generation to the lung community.
Maternal tobacco smoke exposure is associated with impaired fetal growth and long-term disease risk (DOHaD, Developmental Origins of Health and Disease). Whether placental steroid hormones are independently altered remains a matter of debate. We quantified six placental steroids (estradiol, estriol, estrone, progesterone, testosterone, and pregnanediol) using HPLC-Corona CAD in 70 deliveries (C = 30; PS = 20; AS = 20). Distributional differences were assessed with Kruskal-Wallis and pairwise Mann-Whitney tests with Benjamini-Hochberg (BH) control. Adjusted associations used log-linear OLS with HC3 robust SE: Model A (gestational age, maternal BMI, newborn sex) and Model B (Model A + birth weight), reported as percent change vs. controls, computed as (exp(β) - 1) × 100 with 95% CI. Secondary analyses tested (i) multiclass logistic classification of C/PS/AS from the steroid panel (5-fold stratified CV) and (ii) prediction of birth weight (OLS and 2-component PLS). All six steroids differed by group (BH-adjusted p ranging from 9.18 × 10-12 to 6.66 × 10-8). In Model A, AS vs. C showed lower estrogens/progestins (estradiol, -46.2%; estriol, -24.7%; estrone, -25.9%; progesterone, -28.2%; pregnanediol, -31.4%) and higher testosterone (+40.8%); these effects persisted in Model B after adjusting for birth weight. The panel classified C/PS/AS with 0.900 cross-validated accuracy (weighted OvR AUC 0.994). Hormones poorly predicted birth weight (PLS CV R2 = -0.777). Maternal active and passive smoking is associated with a coherent and independent disruption of placental steroidogenesis. A targeted placental steroid panel offers biologically meaningful early markers relevant to DOHaD.
Recent reports suggest that New Zealanders underestimate the burden of non-communicable diseases (NCDs) on society, perceiving NCDs as standalone problems to be managed by affected individuals. This belief conflicts with the Developmental Origins of Health and Disease (DOHaD) hypothesis that NCD risk is rooted in early-life environmental exposures. For the research community to contribute towards shifting societal beliefs, we need to know more about NZers' understanding of how NCDs develop and have the potential to track this over time. To address this, we conducted a face-to-face survey of 702 Auckland adults in 2015-16, repeated in 2022-23 with 814 online and 96 face-to-face respondents. An increased recognition of links between mental health and obesity was the only change observed between the earlier and later cohorts. Overall, of the 59% familiar with the term 'non-communicable disease', 73% accurately described NCD characteristics and gave examples. Online, tertiary-educated and non-male respondents were more likely to identify various social determinants of health in addition to individual behaviours as contributors to metabolic disease risk. More than twice as many subjects strongly agreed that preconception health of mothers could affect the health of the child than that of fathers. Maternal nutrition was recognised by most as important for fetal health, but 49% disagreed or did not know if it could affect adult health. These results indicate that regardless of subject sampling or data collection method, adult New Zealanders have little appreciation of the significance of the early-life environment in relation to NCD risk across the lifespan.
Maternal mental health represents a significant global health burden, not only in terms of maternal wellbeing, but also for the impact it has on child development. The relationship between maternal mental health and deleterious environmental exposures to the fetus is one mechanism of risk transmission. This study utilizes network analysis to a) explore how maternal mental health is associated with a wide array of fetal exposures, and b) examine how these exposures cluster together. A total of 485 pregnant women were recruited from the Mercy Hospital for Women in Melbourne, Australia between 2011-2017, as part of the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). The MPEWS includes measures of mental health diagnosis and symptoms, psychotropic medication, smoking, alcohol, substance use, and a wide range of lifestyle factors in the first and third trimesters of pregnancy. Regularized Partial Correlation Modelling was used to examine the network of relationships between maternal mental health and fetal exposures due to environmental factors, lifestyle and medications. For women diagnosed with mental health disorders there are relatively higher rates of exposure to smoking, anxiety and depression symptoms, psychotropic medications, pregnancy health conditions and less than optimal lifestyle factors. Factors such as physical exercise and folate supplementation show strong patterns of partial correlation. Trait anxiety emerged as the central variable in the network with the highest strength of relationship to all other exposure variables. The current study shows the value of approaching fetal exposures as a complex network of associated aspects of maternal lifestyle, mental health and environment. Viewing exposures together may assist clinical and public health interventions to target multiple associated risk factors, rather than the current focus on individual exposures. The preconception and perinatal periods offer important opportunities for the prevention of teratogenic fetal exposures and the promotion of a healthy start to life.
Research into the Developmental Origins of Health and Disease (DOHaD) has established links between environmental exposures in early life and later-life health outcomes. Emerging interventions typically focus on improving maternal nutrition and neonatal healthcare practices yet often neglect to assess or enhance subject understanding of potential long-term impacts or to communicate the benefits of maximising parental health prior to conception. This study critically evaluates a survey tool developed to measure knowledge of non-communicable diseases (NCDs) and early-life contributors to lifelong health. The rationale behind the wording and format of the questions is examined alongside options for coding and statistical interpretation of the data. Considerations for implementation are discussed, illustrated by key findings arising from tracking of the tool's application in Aotearoa New Zealand over ten years. We demonstrate that the survey tool can be adapted for use in a variety of contexts, producing both quantitative and qualitative baseline data suitable for informing health promotion interventions and monitoring changes in population knowledge. This research also highlights a key difference between awareness of and understanding of scientific concepts and the importance of distinguishing between these when considering public engagement with science.
Several studies have been published studying association between parental low birth weight (BW) and neonatal outcomes of their children. To date no systematic review and meta-analysis (SRM) has been published to quantify the impact of maternal and paternal BW on outcomes in the next generation. The aim of this SRM was to analyse the association between parental BW and anthropometric and metabolic outcomes in their children.Electronic databases were searched for studies documenting BW of parents and children with neonatal outcomes. Primary outcome was to evaluate impact of parental BW on occurrence of LBW in children. Secondary outcomes were to assess impact of parental BW on occurrence of macrosomia, small for gestational age (SGA), preterm labour/delivery, and burden of non-communicable disease in later life.We screened 54,961 articles, data from 14 studies (320,515 parent-child pairs), which fulfilled all criteria, were analysed. Maternal LBW was associated with higher chances of neonatal LBW [odds ratio (OR)1.95 (95% CI:1.56-2.46); P < 0.01; I2 = 91%], neonatal SGA [OR 2.29(95% CI:1.72-3.05); P < 0.01; I2 = 37%], lower chances of neonatal macrosomia [OR 0.50 (95% CI:0.39-0.65); P < 0.01; I2 = 35%] and had no impact on preterm labour/delivery [OR1.20(95% CI:0.67-2.16); P = 0.53; I2 = 88%]. Maternal macrosomia was associated with higher neonatal macrosomia [OR 2.66 (95% CI:2.44-3.16); P < 0.01; I2 = 48%], lower SGA [OR 0.40(95% CI:0.29-0.53); P < 0.01; I2 = 0%] and preterm labour/delivery [OR 0.77 (95% CI:0.63-0.94); P < 0.01; I2 = 4%]. Paternal but not maternal LBW was predictor of metabolic syndrome and diabetes in adulthood.Maternal LBW is an important predictor of LBW and SGA in neonates. Maternal macrosomia is an important predictor of neonatal macrosomia; is protective against SGA and preterm labour/childbirth. Neonatal size of parents is reflected in neonatal size of their children.
Maternal diabetes, a common pregnancy complication, has long-term implications for both mother and offspring. While the developmental origins of metabolic health from prenatal diabetes exposure are well known, cognitive consequences in offspring are still being explored. The timing of hyperglycemia during pregnancy that most affects cognitive development and whether these effects persist into adulthood remains unclear. This study aimed to determine the association between trimester-specific hyperglycemia exposure and adult cognition in the offspring of women with pregestational diabetes. The Transgenerational Effect on Adult Morbidity (TEAM) Study evaluated health outcomes in young adult offspring of mothers with pregestational diabetes who participated in a Diabetes in Pregnancy Program Project Grant (PPG) at the University of Cincinnati (1978-1995). The TEAM Study visit (March 2018 - August 2022) included a comprehensive clinical examination and cognitive assessment (Wechsler Abbreviated Scale of Intelligence - II). Linear regression estimated the association between prenatal hyperglycemia and offspring's perceptual reasoning and verbal comprehension. The mean age at follow-up was 32.1 years. Hyperglycemia during pregnancy was inversely associated with cognitive measures, controlling for confounders including maternal education and pre-pregnancy obesity. Higher glycohemoglobin in the second and third trimesters was significantly linked to lower IQ scores, matrix reasoning, and vocabulary subtest scores. Third-trimester hyperglycemia was also associated with lower block design subtest scores. In summary, hyperglycemia, particularly in the latter half of pregnancy, was associated with lower cognitive ability in adult offspring of women with pre-pregnancy pregestational diabetes.
The obesogenic maternal environment can lead to cardiac hypertrophy in the offspring. The aim of this study was to investigate whether (-)-epicatechin (Epi) modify the expression of genes related to pathological cardiac hypertrophy (CH), and its physiological pathway, in offspring obese by programing. Four groups of eight male offspring Wistar rats of 110 days were randomly selected to control groups [C and offspring of maternal obesity (MO)] or to Epi groups (C + Epi or MO + Epi). In heart tissue, we evaluated the size of the ventricular walls and cavities, presence of fibrosis, mRNA and protein of Myh6, Myh7, Anp, Bnp, Acta 1, Col1a1, Akt, and Mtor. We observed an increase of the heart weight/body ratio in groups treated with Epi. Only in MO group, heart area and its perimeter were increased, as well as Myh7 and Anp mRNA. We found a significant decrease of fibrosis area in male offspring treatment with Epi. In Epi group Anp mRNA was decreased whilst Anp protein in MO group was increased; further, a decrease in Col1a1 protein was found in MO group. In conclusion, the maternal obesity activates pathological CH markers reactivating fetal cardiac genes involved in histological changes observed in cardiac tissue. Epi treatment decreased the content of collagen area and expression of some fetal cardiac genes participating in this pathway in offspring of maternal obesity.
Maternal deficiency of vitamin B12 (B12) is associated with neural tube defects, fetal growth restriction, and future risk of non-communicable disease in the offspring. Little is known about the molecular basis of these associations. We hypothesized that B12 regulates the expression of fetal genes, thereby influencing fetal growth and fetal programming. We investigated the association of B12 and other micronutrient concentrations in the cord blood with gene expression in the cord blood mononuclear cells. We performed a Weighted Gene Co-expression Network Analysis (WGCNA) on cord blood transcriptome of babies born in a pre-conception trial Pune Rural Intervention in Young Adolescents of B12 and multi-micronutrients (MMN). The gene modules (clusters) in WGCNA that showed a significant correlation with cord blood B12 and MMN were subjected to gene ontology (GO) analysis. WGCNA generated 23 different modules. Cord blood B12 concentrations were strongly correlated with modules of genes involved in methylation reactions and gene regulation. Cord B2 concentrations correlated with gene modules associated with demethylation reactions. Vitamins B6 and B9 did not show a unique association either with gene modules or specific GO terms. Our results demonstrate that maternal B12 may regulate expression of fetal genes involved in methylation reaction. This is a novel suggestion for the role of B12 in fetal growth, development, and the Developmental Origins of Health and Disease paradigm.
The impact of maternal nutrition during the peri-conception period on offspring sex remains unclear. Therefore, this study aimed to explore the association between maternal nutritional intake around conception and offspring sex. Data were collected from the Japan Environment and Children's Study, which enrolled 97,510 mother-child pairs. The effect of maternal intake of fats, proteins, and fatty acids on offspring sex was analyzed, adjusting for maternal demographics and lifestyle factors. Overall, maternal intake of total fatty acids, saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), n-3 PUFA, n-6 PUFA, and protein and the ratios of n-6/n-3 and SFA/energy showed no consistent associations with offspring sex.However, further analyses revealed notable patterns related to maternal age and energy intake. Among mothers with high energy intake (≥4,000 kcal/day), higher residual protein intake was associated with increased odds of having a male child (aOR, 1.87; 95% CI, 1.17-2.98). In mothers aged under 20 years, increased n-3 PUFA intake was linked to higher odds of male births, while a higher n-6/n-3 ratio was associated with lower odds of male births. Additionally, among mothers aged 20-35 years, higher n-3 PUFA intake was associated with decreased odds of having a male child (aOR, 0.89; 95% CI, 0.82-0.98).These findings indicate that while no consistent overall relationship was observed, certain maternal nutritional patterns may influence offspring sex, highlighting the need for further research on maternal diet and reproductive outcomes.
Obesity and overweight in pregnant women increase pregnancy and neonatal morbidity with a risk of metabolic syndrome for children in later life. Maternal preconceptional bariatric surgery reduces maternal and paediatric outcomes but may induce fetal nutritional deficiencies and intrauterine growth restriction through placental reprogramming. The aim of this study was to describe feto-placental unit modifications induced by obesity, and the effect of bariatric surgery performed before gestation, on a diet-induced obese rat model. One month after surgery, rats of 'control', 'obese' and 'bariatric surgery' groups were mated and then sacrificed at D19 of gestation. Clinical description, immuno-histochemistry and molecular analyses were performed on feto-placental units. Obesity induces placental modifications including lipid accumulations, increased inflammation and oxidative stress. Some of these modifications are partially restored by maternal preconceptional bariatric surgery. On the other hand, a reduction in the expression of markers of glucose transport, insulin function and amino acid transport, after bariatric surgery was observed. This phenotype may lead to fetal caloric restriction, adoption of a 'thrifty phenotype' and subsequently fetal growth restriction. These preliminary findings highlight the importance of a close follow-up of women who have undergone bariatric surgery and their children.
Adverse prenatal conditions can induce intrauterine growth restriction (IUGR) and increase the risk of adulthood metabolic disease. Mechanisms underlying developmentally programmed metabolic disease remain unclear but may involve disrupted postnatal circadian rhythms and kisspeptin signalling. We investigated the impact of maternal hypoxia-induced IUGR on hypothalamic and hepatic expression of clock genes (Bmal1, Per2 and Reverbα), metabolic genes (Pparα, Pparγ and Pgc1α) and kisspeptin genes (Kiss1 and Kiss1r) in adult offspring. Pregnant BALB/c mice were housed in hypoxic conditions (10.5% oxygen) from gestational day 11 to 17.5 and then returned to normoxic conditions until term (gestational day ∼ 21). Control animals were housed in normoxic conditions throughout pregnancy. Offspring were weighed at birth. At 8 weeks of age, body, liver and brain tissues were collected and weighed. Relative clock gene, metabolic gene and kisspeptin signalling gene expression were measured using qPCR. The IUGR offspring were lighter at birth and remained lighter at 8 weeks but with higher brain relative to body weight. The IUGR offspring had decreased hypothalamic Bmal1 and Reverbα expression, but unchanged hepatic clock gene expression and no change in hypothalamic or hepatic Per2 expression, compared with Control offspring. This tissue-specific change in clock gene expression suggests circadian dysregulation. There were no IUGR-related changes to metabolic gene expression in the hypothalamus or liver, but IUGR offspring had increased hypothalamic Kiss1r expression. These results demonstrate IUGR offspring from hypoxia pregnancies show central circadian misalignment and potentially disrupted hypothalamic Kiss1/Kiss1r signalling, which may contribute to developmentally programmed metabolic disease.
Micro- and nanoplastics (MNPs) pollution has become a global environmental concern due to its widespread presence and diverse sources. These tiny plastic particles, originating from industrial processes, plastic waste degradation, and consumer products, have infiltrated various ecosystems, food chains, and even human tissues. Recent studies indicate that MNPs are not only pervasive in air, water, and soil but also accumulate in the human body through ingestion, inhalation, and dermal exposure. However, the implications of MNPs exposure, particularly during pregnancy, remain poorly understood. Of critical concern is the potential transfer of MNPs and their associated chemical additives across the placental barrier, posing risks to fetal development. In this review, we comprehensively analyze mainstream technologies used for detecting and characterizing MNPs, including spectroscopy- and microscopy-based approaches, as well as emerging detection methods. We also examine recent findings on the toxicity of MNP-associated chemicals, such as endocrine-disrupting compounds and heavy metals, which may have long-term effects on human health. Particular emphasis is placed on how maternal exposure to MNPs could impact offspring development, potentially leading to neurodevelopmental disorders, metabolic disturbances, and immune system dysregulation. Despite growing concerns, research gaps persist regarding the precise mechanisms through which MNPs influence maternal and fetal health. The findings recommend for further multidisciplinary research to assess the long-term consequences of prenatal MNPs exposure. Addressing these uncertainties is crucial for informing public health policies, mitigating risks, and ensuring the well-being of pregnant women and future generations.