Developmental Origins Of Health Research Articles

Developmental origins of health and disease: Impact of paternal nutrition and lifestyle.

Most epidemiological and experimental studies have focused on maternal influences on offspring's health. The impact of maternal undernutrition, overnutrition, hypoxia, and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic, respiratory, endocrine, and reproduction among others. During the past decade, it has become evident that paternal environmental factors are also linked to the development of diseases in offspring. In this article, we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development, health, and disease and explore the mechanisms underlying the paternal programming of offspring health. The available evidence suggests that poor paternal pre-conceptional nutrition and lifestyle, and advanced age can increase the risk of negative outcomes in offspring, via both direct (genetic/epigenetic) and indirect (maternal uterine environment) effects. Beginning at preconception, and during utero and the early life after birth, cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child's health. Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status. However, the evidence is mostly based on animal studies, and well-designed human studies are urgently needed to verify findings from animal data.

Influence of Immune System Abnormalities Caused by Maternal Immune Activation in the Postnatal Period

The developmental origins of health and disease (DOHaD) indicate that fetal tissues and organs in critical and sensitive periods of development are susceptible to structural and functional changes due to the adverse environment in utero. Maternal immune activation (MIA) is one of the phenomena in DOHaD. Exposure to maternal immune activation is a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic diseases, and human immune disorders. It has been associated with increased levels of proinflammatory cytokines transferred from mother to fetus in the prenatal period. Abnormal immunity induced by MIA includes immune overreaction or immune response failure in offspring. Immune overreaction is a hypersensitivity response of the immune system to pathogens or allergic factor. Immune response failure could not properly fight off various pathogens. The clinical features in offspring depend on the gestation period, inflammatory magnitude, inflammatory type of MIA in the prenatal period, and exposure to prenatal inflammatory stimulation, which might induce epigenetic modifications in the immune system. An analysis of epigenetic modifications caused by adverse intrauterine environments might allow clinicians to predict the onset of diseases and disorders before or after birth.

Low glomerular number at birth can lead to the development of chronic kidney disease.

Chronic kidney disease (CKD) prevalence is increasing worldwide, and reducing the number of patients with CKD is of utmost importance. The environment during the fetal, perinatal, and early childhood stages may influence CKD development (developmental origins of health and disease). Under conditions of maternal malnutrition, the glomerular number of infants reduces, and the risk of developing CKD may increase. Nephron progenitor cells and ureteric buds interact with each other to form glomeruli at the tip of the ureteric bud. Thus, the number of glomeruli is determined by the number of ureteric bud branches, which are reportedly decreased due to maternal malnutrition, in turn reducing the glomerular number. Four possible mechanisms can explain the low glomerular number resulting from maternal malnutrition: 1) suppression of c-Ret expression, 2) suppression of nephron formation by renin-angiotensin-aldosterone system inhibition, 3) exposure to excess glucocorticoids, and 4) promotion of apoptosis. Additionally, nephron formation does not continue after birth in humans. Therefore, a low glomerular number at birth is a lifelong burden on the glomeruli and increases the risk of developing CKD. Therefore, it is important to maintain the glomerular number at birth. Accurate glomerular counts are essential for conducting studies on the glomerular number. The dissector/fractionator method is the gold standard; however, it can only be performed at some institutions. Recently, methods have been developed to measure the glomerular number by combining computed tomography and pathological examination and measure the glomerular count using magnetic resonance imaging. Models of decreased and increased glomerular numbers have been developed. Moreover, research regarding the causes of decreased glomerular number and its relationship with development of lifestyle-related diseases and renal dysfunction has significantly progressed, furthering our understanding of the importance of glomerular number.

Hormonal Programming / Imprinting Phenomena as Related to the Liver and Pancreas

A short overview is presented on hormonal programming / imprinting phenomena in liver and pancreas. The main focus is made on some data related to the concept of DOHaD. It is proposed to enhance research efforts in this important area in the near future.Keywords: Programming; Imprinting; Glucocorticoids Abbreviations: CBG: Corticosteroid-Binding Globulin; DOHaD: Developmental Origins of Health and Disease; GC: Glucocorticoids; GH: Growth Hormone; IGFBP: Insulin-like Growth Factor-Binding Proteins; SA: Serum Albumin; TRH: Thyrotropin-Releasing Hormone

Developmental programming of the neuroendocrine axis by steroid hormones: Insights from the sheep model of PCOS.

The reproductive neuroendocrine system is a key target for the developmental programming effects of steroid hormones during early life. While gonadal steroids play an important role in controlling the physiological development of the neuroendocrine axis, human fetuses are susceptible to adverse programming due to exposure to endocrine disrupting chemicals with steroidal activity, inadvertent use of contraceptive pills during pregnancy, as well as from disease states that result in abnormal steroid production. Animal models provide an unparalleled resource to understand the effects of steroid hormones on the development of the neuroendocrine axis and their role on the developmental origins of health and disease. In female sheep, exposure to testosterone (T) excess during fetal development results in an array of reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary responsiveness to gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) hypersecretion, functional hyperandrogenism, multifollicular ovarian morphology, and premature reproductive failure. Similar to a large proportion of women with PCOS, these prenatally T-treated sheep also manifest insulin resistance and cardiovascular alterations, including hypertension. This review article focuses on the effects of prenatal androgens on the developmental programming of hypothalamic and pituitary alterations in the sheep model of PCOS phenotype, centering specifically on key neurons, neuropeptides, and regulatory pathways controlling GnRH and LH secretion. Insights obtained from the sheep model as well as other animal models of perinatal androgen excess can have important translational relevance to treat and prevent neuroendocrine dysfunction in women with PCOS and other fertility disorders.

The Role of Maternal Vitamin D Deficiency in Offspring Obesity: A Narrative Review.

Currently, vitamin D (VD) deficiency during pregnancy is widespread globally, causing unfavorable pregnancy outcomes for both mothers and infants for a longer time than expected, based on the Developmental Origins of Health and Disease (DOHaD) theory. As VD plays a key role in maintaining normal glucose and lipid metabolism, maternal VD deficiency may lead to obesity and other obesity-related diseases among offspring later in life. This review mainly focuses on the effect of maternal VD deficiency on offspring lipid metabolism, reviewing previous clinical and animal studies to determine the effects of maternal VD deficit on offspring obesity and potential mechanisms involved in the progression of offspring obesity. Emerging clinical evidence shows that a low VD level may lead to abnormal growth (either growth restriction or largeness for gestational age) and lipid and glucose metabolism disorders in offspring. Here, we also outline the link between maternal VD deficiency and life-long offspring effects, including the disorder of adipogenesis, the secretion of adipocytokines (including leptin, resistin, and adiponectin), activated systemic inflammation, increased oxidative reactions in adipose tissue, insulin resistance, and abnormal intestinal gut microbiota. Thus, there is an urgent need to take active steps to address maternal VD deficiency to relieve the global burden of obesity.

Exploring the effects of weaning age on adult infectious disease mortality among 18th-19th century Italians.

The developmental origins of health and disease (DOHaD) hypothesis describes how early childhood stress affects morbidity and mortality later in life. The role of early childhood stress in mortality from infectious disease is understudied. Stressors in early childhood that weaken the immune system may result in increased susceptibility to infectious disease in adulthood. Weaning is one of the earliest potential periods of significant stress in early childhood. This research investigates the effect of weaning after ~6months of age on cholera mortality among 18th-19th-century Italian populations by determining if earlier breastfeeding cessation is associated with earlier mortality, analyzing childhood dietary variation and physiological stress markers, and determining if age-at-weaning completion differs between catastrophic and attritional populations. Serial dentin stable carbon and nitrogen isotope analyses from canines are compared between catastrophic (n=45) and attritional groups (n=23). Canines are sectioned serially from crown to apex, and the increment's δ15 N and δ13 C are used to estimate age-at-weaning completion. Catastrophic and attritional groups exhibit similar age-at-weaning completion (~2.8 years). Seventy-four percent of individuals lack elevated δ15 N values in dentin that formed during infancy. Age-at-weaning completion was not a predisposing factor in cholera mortality in adulthood in this sample. Age-at-weaning completion may not be significantly associated with infectious disease mortality because weaning completion likely occurred after infants had adapted to consuming contaminated weanling foods. Individuals without detectable weaning curves may represent infants who received supplementary foods since birth or were weaned before the age of 6-9months.

Beyond the Gut, Emerging Microbiome Areas of Research: A Focus on Early-Life Microbial Colonization.

Undoubtedly, the human body harbors trillions of microbes of different kinds performing various physiological activities, such as priming the immune system, influencing host metabolism, and improving health by providing important metabolites such as short-chain fatty acids. Although the gut is considered the "microbial organ" of our body as it hosts the most microbes, there are microbes present in various other important anatomical locations differing in numbers and type. Research has shown the presence of microbes in utero, sparking a debate on the "sterile womb" concept, and there is much scope for more work in this area. It is important to understand the early-life microbiome colonization, which has a role in the developmental origins of health and disease in later life. Moreover, seminal studies have indicated the presence of microbes beyond the gut, for example, in the adipose tissue and the liver. However, it is still unclear what is the exact source of these microbes and their exact roles in health and disease. In this review, we appraise and discuss emerging microbiome areas of research and their roles in metabolic health. Further, we review the importance of the genital microbiome in early-life microbial interactions.

Developmental origins of health and disease: knowledge, attitude and practice of obstetrics & gynecology residents, pediatric residents, and medical students

ABSTRACT Developmental Origin of Health and Disease (DOHaD) explains how the health of the mother influences the offspring’s risk of non-communicable diseases in later life. However, this remains underutilized in clinical practice. This study aimed to investigate the knowledge, attitude, and practice (KAP) of medical students, Obstetrics and Gynecology (O&G) and Pediatrics residents, toward DOHaD, identify potential barriers to DOHaD counseling, and translate DOHaD concepts into clinical practice. This cross-sectional study was conducted with a multi-section digital questionnaire, rated on a five-point Likert scale (1–5), with a higher score indicating better KAP. The scores between groups were compared using ANOVA. A total of 117 participants, comprising medical students (n = 75, 64.1 percent), O&G (n = 33, 28.2 percent) and Pediatric residents (n = 9, 7.7 percent), completed the questionnaire. The mean scores for the “Knowledge,” “Attitude” and “Practice” sections were 3.73 (standard deviation 0.82), 4.27 (0.59) and 3.03 (0.52), respectively. O&G residents scored higher for the “Practice” section than Pediatric residents (mean scores 3.17 vs. 2.16; p = .048). Overall, the participants demonstrated good knowledge and attitude, but poor practice toward DOHaD. Thus, there is a need to improve education and training for health care professionals, develop a structured implementation framework, and provide a transdisciplinary care continuum for mother and child.

Low birthweight is associated with epigenetic age acceleration in the first 3 years of life.

The Developmental Origins of Health and Disease hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality. Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age 3. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration. Chronological age was highly correlated with epigenetic age from birth to age 3 (r = 0.95, p < 2.2 × 10-16). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 g, predicted epigenetic age acceleration over the first 3 years of life (b = -0.39, p = 0.005). Our longitudinal analysis provides the first evidence for accelerated epigenetic aging that emerges between birth and age 3 and associates with low birthweight. These results suggest that early life experiences, such as low birthweight, may shape the trajectory of epigenetic aging in early childhood. Furthermore, accelerated epigenetic aging may be a pathway that links low birthweight and poor adult health outcomes.

Nephron deficit and low podocyte density increase risk of albuminuria and glomerulosclerosis in a model of diabetes.

Podocytes are terminally differentiated epithelial cells in glomeruli. Podocyte injury and loss are features of many diseases leading to chronic kidney disease (CKD). The developmental origins of health and disease hypothesis propose an adverse intrauterine environment can lead to CKD later in life, especially when a second postnatal challenge is experienced. The aim of this study was to examine whether a suboptimal maternal environment would result in reduced podocyte endowment, increasing susceptibility to diabetes-induced renal injury. Female C57BL/6 mice were fed a low protein diet (LPD) to induce growth restriction or a normal protein diet (NPD) from 3 weeks before mating until weaning (postnatal Day 21, P21) when nephron and podocyte endowment were assessed in one male and one female offspring per litter. Littermates were administered streptozotocin or vehicle at 6 weeks of age. Urinary albumin excretion, glomerular size, and podometrics were assessed following 18 weeks of hyperglycemia. LPD offspring were growth restricted and had lower nephron and podocyte number at P21. However, by 24 weeks the podocyte deficit was no longer evident and despite low nephron endowment neither albuminuria nor glomerulosclerosis were observed. Podocyte number was unaffected by 18 weeks of hyperglycemia in NPD and LPD offspring. Diabetes increased glomerular volume reducing podocyte density, with more pronounced effects in LPD offspring. LPD and NPD diabetic offspring developed mild albuminuria with LPD demonstrating an earlier onset. LPD offspring also developed glomerular pathology. These findings indicate that growth-restricted LPD offspring with low nephron number and normalized podocyte endowment were more susceptible to alterations in glomerular volume and podocyte density leading to more rapid onset of albuminuria and renal injury than NPD offspring.

PS-B05-9: ADVANCED MATERNAL AGED MOUSE MODEL SHOWED FETAL GROWTH RESTRICTION AND WOULD BE A MODEL FOR DOHAD

Backgrounds: The number of advance-aged pregnancies, defined as those over 35 years of age, has been increasing in developed countries due to tendency to marry later with women's social advancement and assisted reproductive technology. Furthermore, in Japan, the incidence of hypertensive disorders of pregnancy over 40 years of age is as high as approximately 8%, which have a high rate of premature births and low birth weight, and fewer nephrons. Recently, based on the developmental origins of health and disease (DOHaD) hypothesis, it has been recognized that the risk of developing hypertension, proteinuria and renal failure in the future is increased in aged pregnancies. However, the detailed mechanism is uncertain. Methods: Female ICR mice of 6 to 10 months (Advanced maternal age, AMA group) and of 10 to 12 weeks (Control; CON group) were mated with males of 10 to 16 weeks. Blood pressure during pregnancy on day 7 and 14 was measured in both groups (n = 4, n = 4). The pups born in both groups (AMA, n = 4–13; CON, n = 10–16) were weighed at postnatal day 0, a week, 4 weeks, and 8 weeks of age. Blood pressure (n = 7, n = 3) at 8 weeks of age was measured using the tail-cuff technique. The results were compared using the Mann-Whitney U test. Results: There was no difference in blood pressure during pregnancy on day 7 and day 14 in both groups. In the AMA mouse model, the weights of postnatal day 0 pups were significantly lower (AMA vs. CON, 1.66 ± 0.22 g vs. 1.9 ± 0.22 g, P = 0.006). However, no difference was found between the two groups at a week and 4 weeks. Conversely, the body weights of the AMA model were significantly higher at 8 weeks of age (AMA vs. CON, 47.7 ± 3.43 g vs. 45.4 ± 2.8 g, P = 0.041) and the systolic blood pressure in the AMA group tended to be higher. Discussion/Conclusion: In the present study, the AMA mouse model induced fetal growth restriction and subsequently showed catch-up growth. Furthermore, their pups’ weights were significantly higher and elevated blood pressure was observed at adult age. While previous animal models of DOHaD have been mainly based on studies of dietary restriction, chemical exposure, and preeclampsia, this model showed similar symptoms to DOHaD models.

An evolutionary perspective on the association between grandmother-mother relationships and maternal mental health among a cohort of pregnant Latina women.

Grandmothers are often critical helpers during a mother's reproductive career. Studies on the developmental origins of health and disease demonstrate how maternal psychological distress can negatively influence fetal development and birth outcomes, highlighting an area in which soon-to-be grandmothers (henceforth "grandmothers") can invest to improve both mother and offspring well-being. Here, we examine if and how a pregnant woman's mental health- specifically, depression, state-anxiety, and pregnancy-related anxiety- is influenced by her relationship with her fetus' maternal and paternal grandmother, controlling for relationship characteristics with her fetus' father. In a cohort of pregnant Latina women in Southern California (N = 216), we assessed social support, geographic proximity, and communication between the fetus' grandmothers and pregnant mother. We assessed maternal mental health with validated questionnaire-based instruments. We find that both social support from and communication with the maternal grandmother were statistically associated with less depression, while no paternal grandmother relationship characteristics were statistically significant in association with any mental health variable. These results align with the idea that maternal grandmothers are more adaptively incentivized to invest in their daughters' well-being during pregnancy than paternal grandmothers are for their daughters-in-law. Results suggest that the positive association of maternal grandmothers with mothers' mental health may not hinge on geographic proximity, but rather, potentially function through emotional support. This work represents a novel perspective describing a psychological and prenatal grandmaternal effect.

Developmental exposure to thyroid disruptors: misprogramming of the brain's stem cells in later life?

Developmental exposure to thyroid disruptors: misprogramming of the brain's stem cells in later life?

Integrating evolutionary, developmental and physiological mismatch.

Contemporary evolutionary medicine has unified the idea of 'evolutionary mismatch', derived from the older idea of 'adaptive lag' in evolution, with ideas about the mismatch in development and physiology derived from the Developmental Origins of Health and Disease (DOHaD) paradigm. A number of publications in evolutionary medicine have tried to make this theoretical framework explicit. The integrative theory of mismatch captures how organisms track environments across space and time on multiple scales in order to maintain an adaptive match to the environment, and how failures of adaptive tracking lead to disease. In this review, we try to present this complex body of theory as clearly and simply as possible with the aim of facilitating its application in new domains. We introduce terminology, which is as far as possible consistent with earlier usage, to distinguish the different forms of mismatch. Mismatch in its modern form is a productive organizing concept that can help researchers articulate how physiology, development and evolution interact with one another and with environmental change to explain health outcomes.

EARLY-LIFE EXPOSURE TO THE CHINESE FAMINE OF 1959–1961 AND LATER-LIFE HEALTH: EARLY LIFE AS A CRITICAL PERIOD

Abstract Barker’s fetal origins hypothesis and the critical period theory suggest that early life events have long-term health effects. However, evidence of the famine exposure in early life and its effects on health in later life is scarce and inconsistent. To explore the effects of early-life exposure to the Chinese famine of 1959-1961 on later-life multimorbidity, we performed Poisson growth curve models using CHARLS Life History 2014 and CHARLS 2011-2018 (42,775 observations from 12,060 respondents). Our analyses revealed two findings. First, there was an overall detrimental effect of the early-life famine exposure on multimorbidity, although there was no effect of severity of famine exposure. Second, there was no overall interaction between famine exposure and life stages, although a more parsimonious model suggested that the detrimental effect of famine exposure was more pronounced in earlier life stages than in later life stages. Findings suggest that early life is a critical period in the life course and provides developmental origins of health and disease in later life.

MiR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach.

The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.

Gestational exposure to triphenyl phosphate induces epigenetic modifications in C57Bl/6 fetal liver.

Triphenyl phosphate (TPHP) is a chemical flame retardant and plasticizer which is added to consumer and industrial products. The developmental origins of health and disease hypothesis postulate that in utero exposures can have later-in-life effects on the developing fetus and can alter fetal gene expression. This study aimed to determine whether epigenetic modifications occurred following in utero TPHP exposure in mice and whether these changes were dose and/or sex-dependent. Pregnant C57Bl/6 mice were treated with 0, 5, 25, or 50 mg/kg of TPHP on gestational days (GD) 8, 10, 12, and 14 via intraperitoneal injection and fetal livers were collected on GD 19. Changes in the levels of acetylation of H3 and H4, as well as methylation of H3K9 and global DNA methylation were assessed in the fetal livers by western blot. Results showed that there was a significant decrease in fetal DNA methylation following in utero exposure to 50 mg/kg TPHP compared to the control (0mg/kg) independent of the sex of the fetus. While there were no significant alterations compared to controls in any histone modifications at any dose or sex following in utero TPHP exposure, we did note a decrease (t test, p= .025) in the levels of acetylated H3 in males versus females following a maternal dose of 25 mg/kg. The monomethylated H3K9 levels were also increased in females versus males following exposure to TPHP at 5mg/kg (p= .018) and 25 mg/kg (p= .027) when analyzed via unpaired t tests, although not significantly different from controls. The results suggest that gestational TPHP exposure can induce epigenetic modifications in murine fetal tissue. Specifically, global DNA methylation levels were downregulated in response to TPHP. Additionally, males appear to be more sensitive to TPHP-induced histone modifications than females. These data support the need for further studies investigating the impacts of gestational TPHP exposure on the developing fetus.

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism.

Early life nutrition is associated with the development and metabolism in later life, which is known as the Developmental Origin of Health and Diseases (DOHaD). Epigenetics have been proposed as an important explanation for this link between early life malnutrition and long-term diseases. Non-coding RNAs (ncRNAs) may play a role in this epigenetic programming. The expression of ncRNAs (such as long non-coding RNA H19, microRNA-122, and circular RNA-SETD2) was significantly altered in specific tissues of offspring exposed to maternal malnutrition. Changes in these downstream targets of ncRNAs lead to abnormal development and metabolism. This review aims to summarize the existing knowledge on ncRNAs linking the maternal nutrition condition and offspring metabolic diseases, such as obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD).

Severe maternal stress alters placental function, resulting in adipose tissue and liver dysfunction in offspring of mice

The developmental origins of health and disease (DOHaD) hypothesis is that future lifestyle diseases in offspring are associated with intrauterine origins in the mother; stress during pregnancy is a risk factor for these diseases in offspring. This study aimed to clarify association of maternal stress with placental dysfunction and offspring development in mice. We applied water stress for 24 h during late pregnancy to explore the metabolic response of offspring to a normal diet (ND) and high-fat diet (HFD). Placental functions were altered by maternal stress, reducing the birth weight of the offspring. In the later life of offspring fed with ND, maternal stress impaired systemic glucose tolerance and altered adipokine secretion in adipose tissue and/or liver. The female offspring of stress-induced dams were light in body weight with lower adipose tissue and smaller adipocytes in both the ND and HFD groups. Abnormal situations, such as dysregulation of plasma glucose levels and fatty liver despite and lower increases in body weight, were observed in the female offspring of stress-induced dams, especially in the HFD-treated group. These findings suggest that long-lasting abnormal conditions and responses to metabolic challenges in maternal stress-induced offspring are linked to placental dysregulation and fetal programming.