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International Journal of Molecular... May 2020Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that... (Review)
Review
Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that can either resolve quickly (i.e., acute inflammation) or remain prolonged and unabated (i.e., chronic inflammation). Perhaps less well-appreciated is the importance of inflammatory processes central to healthy pregnancy, including implantation, early stages of placentation, and parturition. Pregnancy juxtaposed with disease can lead to the perpetuation of aberrant inflammation that likely contributes to or potentiates maternal morbidity and poor fetal outcome. Maternal obesity, a prevalent condition within women of reproductive age, associates with increased risk of developing multiple pregnancy disorders. Importantly, chronic low-grade inflammation is thought to underlie the development of obesity-related obstetric and perinatal complications. While diverse subsets of uterine immune cells play central roles in initiating and maintaining healthy pregnancy, uterine leukocyte dysfunction as a result of maternal obesity may underpin the development of pregnancy disorders. In this review we discuss the current knowledge related to the impact of maternal obesity and obesity-associated inflammation on uterine immune cell function, utero-placental establishment, and pregnancy health.
Topics: Animals; Female; Humans; Inflammation; Models, Biological; Obesity, Maternal; Placenta; Pregnancy; Uterus
PubMed: 32471078
DOI: 10.3390/ijms21113776 -
International Journal of Molecular... Feb 2021Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a... (Review)
Review
Overweight and obesity during pregnancy have been associated with increased birth weight, childhood obesity, and noncommunicable diseases in the offspring, leading to a vicious transgenerational perpetuating of metabolic derangements. Key components in intrauterine developmental programming still remain to be identified. Obesity involves chronic low-grade systemic inflammation that, in addition to physiological adaptations to pregnancy, may potentially expand to the placental interface and lead to intrauterine derangements with a threshold effect. Animal models, where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS) resembling the obesity-induced immune profile, showed increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. Cytokine levels might be specifically important for the metabolic imprinting, as cytokines are transferable from maternal to fetal circulation and have the capability to modulate placental nutrient transfer. Maternal inflammation may induce metabolic reprogramming at several levels, starting from the periconceptional period with effects on the oocyte going through early stages of embryonic and placental development. Given the potential to reduce inflammation through inexpensive, widely available therapies, examinations of the impact of chronic inflammation on reproductive and pregnancy outcomes, as well as preventive interventions, are now needed.
Topics: Animals; Child; Child Development; Disease Models, Animal; Female; Fetal Development; Humans; Inflammation; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Metabolic Networks and Pathways; Obesity, Maternal; Pediatric Obesity; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 33572203
DOI: 10.3390/ijms22041732 -
Brain, Behavior, and Immunity May 2022The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born...
The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet's effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (β = -0.622, p < 0.01), adiposity (β = 0.593, p < 0.01), and length of gestation (β = 0.164, p < 0.05) but not with maternal chemokines (β = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (β = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (β = -0.389, p < 0.01) and chemokines (β = -0.298, p < 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (β = -0.426, p < 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.
Topics: Adiposity; Animals; Chemokines; Cytokines; Diet; Diet, High-Fat; Female; Humans; Inflammation; Obesity; Obesity, Maternal; Pregnancy; Prenatal Exposure Delayed Effects; Primates
PubMed: 35217175
DOI: 10.1016/j.bbi.2022.02.024 -
Current Genomics Sep 2019Maternal obesity and maternal overnutrition, can lead to epigenetic alterations during pregnancy and these alterations can influence fetal and neonatal phenotype which... (Review)
Review
BACKGROUND
Maternal obesity and maternal overnutrition, can lead to epigenetic alterations during pregnancy and these alterations can influence fetal and neonatal phenotype which increase the risk of metabolic disorders in later stages of life.
OBJECTIVE
The effects of maternal obesity on fetal programming and potential mechanisms of maternal epigenetic regulation of gene expression which have persistent effects on fetal health and development were investigated.
METHODS
Review of the literature was carried out in order to discuss the effects of maternal obesity and epigenetic mechanisms in fetal programming of metabolic disorders. All abstracts and full-text articles were examined and the most relevant articles were included in this review.
RESULTS
Maternal obesity and maternal overnutrition during fetal period has important overall effects on long-term health. Maternal metabolic alterations during early stages of fetal development can lead to permanent changes in organ structures, cell numbers and metabolism. Epigenetic modifications (DNA methylation, histone modifications, microRNAs) play an important role in disease susceptibility in the later stages of human life. Maternal nutrition alter expression of hypothalamic genes which can increase fetal and neonatal energy intake. Epigenetic modifications may affect the increasing rate of obesity and other metabolic disorders worldwide since the impact of these changes can be passed through generations.
CONCLUSION
Weight management before and during pregnancy, together with healthy nutritional intakes may improve the maternal metabolic environment, which can reduce the risks of fetal programming of metabolic diseases. Further evidence from long-term follow-up studies are needed in order to determine the role of maternal obesity on epigenetic mechanisms.
PubMed: 32476999
DOI: 10.2174/1389202920666191030092225 -
The Journal of Physiology Jul 2022Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk, but its effect on myocardial metabolism is unknown. We...
Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk, but its effect on myocardial metabolism is unknown. We hypothesized that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day (E) 18.5; term ≈ E21), and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor gamma (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction worsened progressively with age in female, but not male, offspring of obese dams, in comparison to age-matched control animals. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese dams than control dams and was correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or F-fluorodeoxyglucose uptake in males and did not alter cardiac H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero might underpin programmed cardiac impairments mechanistically and contribute to cardiovascular disease risk in children of women with obesity. KEY POINTS: Obesity in pregnant women causes cardiac dysfunction in the fetus and increases lifelong cardiovascular disease risk in the offspring. In this study, we showed that maternal obesity in mice induces hypertrophy of the fetal heart in association with altered expression of genes related to nutrient metabolism. Maternal obesity also alters cardiac metabolism of carbohydrates and lipids in the adult offspring. The results suggest that overnutrition in utero might contribute to increased cardiovascular disease risk in children of women with obesity.
Topics: Adult Children; Animals; Cardiomegaly; Cardiovascular Diseases; Carnitine; Female; Fetal Heart; Heart Diseases; Humans; Lipids; Male; Mice; Obesity; Obesity, Maternal; Overnutrition; PPAR gamma; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 35545608
DOI: 10.1113/JP282462 -
The Proceedings of the Nutrition Society Sep 2022There is an ever increasing prevalence of maternal obesity worldwide such that in many populations over half of women enter pregnancy either overweight or obese. This... (Review)
Review
There is an ever increasing prevalence of maternal obesity worldwide such that in many populations over half of women enter pregnancy either overweight or obese. This review aims to summarise the impact of maternal obesity on offspring cardiometabolic outcomes. Maternal obesity is associated with increased risk of adverse maternal and pregnancy outcomes. However, beyond this exposure to maternal obesity during development also increases the risk of her offspring developing long-term adverse cardiometabolic outcomes throughout their adult life. Both human studies and those in experimental animal models have shown that maternal obesity can programme increased risk of offspring developing obesity and adipose tissue dysfunction; type 2 diabetes with peripheral insulin resistance and β-cell dysfunction; CVD with impaired cardiac structure and function and hypertension via impaired vascular and kidney function. As female offspring themselves are therefore likely to enter pregnancy with poor cardiometabolic health this can lead to an inter-generational cycle perpetuating the transmission of poor cardiometabolic health across generations. Maternal exercise interventions have the potential to mitigate some of the adverse effects of maternal obesity on offspring health, although further studies into long-term outcomes and how these translate to a clinical context are still required.
Topics: Humans; Adult; Animals; Female; Pregnancy; Obesity, Maternal; Diabetes Mellitus, Type 2; Obesity; Pregnancy Outcome; Cardiovascular Diseases; Prenatal Exposure Delayed Effects
PubMed: 35974421
DOI: 10.1017/S0029665122001914 -
Pediatric Obesity Sep 2022Maternal obesity is an important determinant of offspring obesity risk, which may be mediated via changes in the infant microbiome. (Clinical Trial)
Clinical Trial
BACKGROUND
Maternal obesity is an important determinant of offspring obesity risk, which may be mediated via changes in the infant microbiome.
OBJECTIVES
We examined infant faecal microbiome, short-chain fatty acids (SCFA), and maternal human milk oligosaccharides (HMO) in mothers with overweight/obese body mass index (BMI) (OW) compared with normal weight (NW) (Clinicaltrials.gov NCT01131117).
METHODS
Infant stool samples at 1, 6, and 12 months were analysed by 16S rRNA sequencing. Maternal (BODPOD) and infant (quantitative nuclear magnetic resonance [QMR]) adiposity were measured. HMOs at 2 months postpartum and faecal SCFAs at 1 month were also assessed. Statistical analyses included multivariable and mixed linear models for assessment of microbiome diversity, composition, and associations of taxonomic abundance with metabolic and anthropometric variables.
RESULTS
At 1 month, offspring of women with obesity had lower abundance of SCFA-producing bacteria (including Ruminococcus and Turicibacter) and lower faecal butyric acid levels. Lachnospiraceae abundance was lower in OW group at 6 months, and infant fat mass was negatively associated with the levels of Sutterella. Gradient boosting machine models indicated that higher α-diversity and specific microbial taxa at 1 month predicted elevated adiposity at 12 months with overall accuracy of 76.5%. Associations between maternal HMO concentrations and infant bacterial taxa differed between NW and OW groups.
CONCLUSIONS
Elevated maternal BMI is associated with relative depletion of butyrate-producing microbes and faecal butyrate in the early infant faecal microbiome. Overall microbial richness may aid in prediction of elevated adiposity in later infancy.
Topics: Bacteria; Butyrates; Female; Gastrointestinal Microbiome; Humans; Infant; Milk, Human; Obesity; Obesity, Maternal; Oligosaccharides; Pregnancy; RNA, Ribosomal, 16S
PubMed: 35478493
DOI: 10.1111/ijpo.12921 -
Clinical Infectious Diseases : An... Nov 2021Maternal overweight and obesity are related to risks of pregnancy and delivery complications that, in turn, are associated with newborn infections. We examined the...
BACKGROUND
Maternal overweight and obesity are related to risks of pregnancy and delivery complications that, in turn, are associated with newborn infections. We examined the associations between early pregnancy body mass index (BMI; kg/m2) and risk of early-onset neonatal bacterial sepsis (EOS).
METHODS
We conducted a nationwide population-based retrospective cohort study of 1 971 346 live singleton infants born in Sweden between 1997 and 2016. Outcome was a culture-confirmed EOS diagnosis. We estimated hazard ratios (HR) of EOS according to BMI using proportional hazard models, and identified potential mediators. Among term infants, we conducted sibling-controlled analyses.
RESULTS
EOS risk per 1000 live births was 1.48; 0.76 in term and 15.52 in preterm infants. Compared with infants of normal-weight mothers (BMI, 18.5-24.9), the adjusted HR (95% confidence interval [CI]) of EOS for BMI categories <18.5, 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40.0 were, respectively, 1.07 (.83-1.40), 1.19 (1.08-1.32), 1.70 (1.49-1.94), 2.11 (1.73-2.58), and 2.50 (1.86-3.38). Maternal overweight and obesity increased the risk of EOS by group B Streptococcus, Staphylococcus aureus, and Escherichia coli. Half of the association was mediated through preeclampsia, cesarean section delivery, and preterm delivery. A dose-response association was consistently apparent in term infants only. In sibling-controlled analyses, every kilogram per meter squared interpregnancy BMI change was associated with a mean 8.3% increase in EOS risk (95% CI, 1.7%-15.3%; P = .01).
CONCLUSIONS
Risk of EOS increases with maternal overweight and obesity severity, particularly in term infants.
Topics: Body Mass Index; Cesarean Section; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Neonatal Sepsis; Obesity, Maternal; Pregnancy; Pregnancy Complications; Retrospective Studies; Risk Factors; Siblings
PubMed: 32770206
DOI: 10.1093/cid/ciaa783 -
The American Journal of Clinical... Apr 2021
Topics: Body Mass Index; Child; Female; Humans; Milk, Human; Obesity, Maternal; Pediatric Obesity; Pregnancy; Regression Analysis
PubMed: 33742200
DOI: 10.1093/ajcn/nqab009 -
Scientific Reports Mar 2020We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of... (Comparative Study)
Comparative Study
We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of pregnant women in Paris (n = 9,579). Adjusted path analysis logistic regression models were used to assess the role of pre-pregnancy obesity as a mediator in the association between maternal place of birth and the development of severe pre-eclampsia. We calculated 1. adjusted odds ratios and 95% confidence intervals for the total exposure-outcome association and for the direct and indirect/obesity-mediated components 2. the indirect/obesity-mediated effect. Ninety-five (0.99%) women developed severe pre-eclampsia, 47.6% were non-European immigrants, 16.3% were born in Sub-Saharan Africa, and 12.6% were obese (BMI > = 30 kg/m). Women experiencing severe pre-eclampsia were more likely to be from Sub-Saharan Africa (p = 0.023) and be obese (p = 0.048). Mothers from Sub-Saharan Africa had an increased risk of severe pre-eclampsia compared to European-born mothers (aOR 2.53, 95% CI 1.39-4.58) and the obesity-mediated indirect effect was 18% of the total risk (aOR 1.18, 95%CI 1.03-1.35). In conclusion, Sub-Saharan African immigrant women have a two-fold higher risk of developing severe pre-eclampsia as compared to European-born women, one-fifth of which is mediated by pre-pregnancy obesity. Our results quantify the potential benefit of decreasing obesity among at-risk women.
Topics: Adult; Africa South of the Sahara; Africa, Northern; Emigrants and Immigrants; Europe; Female; Humans; Maternal Age; Obesity, Maternal; Paris; Poverty Areas; Pre-Eclampsia; Pregnancy; Risk; Urban Population; Young Adult
PubMed: 32251320
DOI: 10.1038/s41598-020-62032-9