Obesity In Pregnancy Research Articles

Programming of cardiometabolic health: the role of maternal and fetal hyperinsulinaemia.

Obesity and gestational diabetes during pregnancy have multiple short- and long-term consequences for both mother and child. One common feature of pregnancies complicated by maternal obesity and gestational diabetes is maternal hyperinsulinaemia, which has effects on the mother and her adaptation to pregnancy. Even though insulin does not cross the placenta insulin can act on the placenta as well affecting placental growth, angiogenesis and lipid metabolism. Obese and gestational diabetic pregnancies are often characterised by maternal hyperglycaemia resulting in exposure of the fetus to high levels of glucose, which freely crosses the placenta. This leads to stimulation of fetal ß-cells and insulin secretion in the fetus. Fetal hyperglycaemia/hyperinsulinaemia has been shown to cause multiple complications in fetal development, such as altered growth trajectories, impaired neuronal and cardiac development and early exhaustion of the pancreas. These changes could increase the susceptibility of the offspring to develop cardiometabolic diseases later in life. In this review, we aim to summarize and review the mechanisms by which maternal and fetal hyperinsulinaemia impact on (i) maternal health during pregnancy; (ii) placental and fetal development; (iii) offspring energy homeostasis and long-term cardiometabolic health; (iv) how interventions can alleviate these effects.

The Edmonton Obesity Staging System and pregnancy outcomes in women with overweight or obesity: A secondary analysis of a randomized controlled trial.

SummaryThe Edmonton Obesity Staging System (EOSS) is a proposed clinical practice tool to determine obesity severity. In a secondary analysis of the Pregnancy Exercise and Research Study (PEARS) (a mobile‐health‐supported lifestyle intervention among pregnant women with body mass index [BMI] ≥25 kg/m2), we apply the EOSS and explore relationships with pregnancy outcomes. In early (14–16 weeks) and late (28 weeks) pregnancy, fasting lipids and glucose were measured, blood pressure was extracted from medical records and maternal well‐being was assessed using the WHO‐5 Well‐being Index. Pearson's correlations, chi‐square statistics and multiple logistic regression were used to identify relationships. One‐way analysis of variance was used to compare groups. Pregnant women (n = 348) were mean (SD) age 32.44 (4.39) years and median (interquartile range) BMI 28.0 (26.57, 29.88) kg/m2. Using metabolic criteria only, 81.9% and 98.9% had raised EOSS scores in early and late pregnancy. From early to late pregnancy, EOSS scores increased by 60.1%. Of these, 10.5% experienced a 2‐point increase, moving from stage 0 to stage 2. There was a potential relationship between early EOSS and large for gestational age (χ 2 = 6.42, df (2), p = .04), although significance was lost when controlled for confounders (p = .223) and multiple testing. Most women with BMI ≥25 kg/m2 had raised EOSS scores, limiting the clinical utility of the tool.

A mouse model of gestational diabetes shows dysregulated lipid metabolism post-weaning, after return to euglycaemia

BackgroundGestational diabetes is associated with increased risk of type 2 diabetes mellitus and cardiovascular disease for the mother in the decade after delivery. However, the molecular mechanisms that drive these effects are unknown. Recent studies in humans have shown that lipid metabolism is dysregulated before diagnosis of and during gestational diabetes and we have shown previously that lipid metabolism is also altered in obese female mice before, during and after pregnancy. These observations led us to the hypothesis that this persistent dysregulation reflects an altered control of lipid distribution throughout the organism.MethodsWe tested this in post-weaning (PW) dams using our established mouse model of obese GDM (high fat, high sugar, obesogenic diet) and an updated purpose-built computational tool for plotting the distribution of lipid variables throughout the maternal system (Lipid Traffic Analysis v2.3).ResultsThis network analysis showed that unlike hyperglycaemia, lipid distribution and traffic do not return to normal after pregnancy in obese mouse dams. A greater range of phosphatidylcholines was found throughout the lean compared to obese post-weaning dams. A range of triglycerides that were found in the hearts of lean post-weaning dams were only found in the livers of obese post-weaning dams and the abundance of odd-chain FA-containing lipids differed locally in the two groups. We have therefore shown that the control of lipid distribution changed for several metabolic pathways, with evidence for changes to the regulation of phospholipid biosynthesis and FA distribution, in a number of tissues.ConclusionsWe conclude that the control of lipid metabolism is altered following an obese pregnancy. These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease.

Reproductive outcomes after bariatric surgery in women.

The presence of obesity may significantly influence female fertility through various mechanisms. Impairment of the hypothalamic-pituitary-ovarian axis in obese women may induce anovulation and infertility. Obesity may have an effect on women’s spontaneous and assisted conception rates, increased miscarriage rates, premature labor, stillbirth and perinatal risks, and menstrual irregularity. It has been suggested that weight loss improves reproductive outcomes due to fertility amelioration and an improvement in menstrual irregularity and ovulation. It is still not known which weight reduction procedures (changes in lifestyle, pharmacological management or bariatric intervention) result in optimal outcome on infertility. Currently, bariatric surgery is defined as the best available method for the management of obesity and its associated diseases.We have analyzed literature facts about effects of bariatric surgery on the function of the hypothalamic-pituitary-ovarian axis, polycystic ovary syndrome (PCOS), anti-Mullerian hormone (AMH) and sexual dysfunction in obesity and pregnancy in obesity. Immediate positive effects of bariatric surgery are evident at the moment, while for long-term outcomes more prolonged follow-up investigations should be done.

Developmental programming by maternal obesity: Lessons from animal models.

The obesity epidemic has led to more women entering pregnancy overweight or obese. In addition to adverse short-term outcomes, maternal obesity and/or gestational diabetes predispose offspring to developing obesity, type 2 diabetes and cardiovascular disease in adulthood through developmental programming. Human epidemiological studies, although vital in identifying associations, are often unable to address causality and mechanistic studies can be limited by the lack of accessibility of key metabolic tissues. Furthermore, multi-generational studies take many years to complete. Integration of findings from human studies with those from animal models has therefore been critical in moving forward this field that has been termed the 'Developmental Origins of Health and Disease'. This review summarises the evidence from animal models and highlights how animal models provide valuable insight into the maternal factors responsible for developmental programming, potential critical developmental windows, sexual dimorphism, molecular mechanisms and age-related offspring outcomes throughout life. Moreover, we describe how animal models are vital to explore clinically relevant interventions to prevent adverse offspring outcomes in obese or glucose intolerant pregnancy, such as antioxidant supplementation, exercise and maternal metformin treatment.

Association between gestational period and obesity in children with the use of dermatoglyphic traits: A preliminary study.

Events occurring during the gestational period can influence the development of diseases and conditions such as obesity. This study aimed to analyze the association between events occurring in the gestational period and the occurrence of obesity in children based on dermatoglyphic traits. The sample comprised 73 children born in 2009, living in Palhoça, Santa Catarina (SC), Brazil, regularly enrolled in public and private schools in that municipality and who are participants of an ongoing major cohort study project called Coorte Brasil Sul. The results show predictive traits of obesity when comparing BMI and fingerprint groups. Obese male group, presented the figure Ulnar Loop (UL) in the right hand (MDT1) thumb and greater number of ridges in the (MDSQL1) right thumb the greater the BMI; likewise, the older the woman getting pregnant the greater the number of ridges that the child presented in the (MESQL2) left index finger and (MESQL1) right thumb. The results obtained infer the presence of predictive traits of BMI ranges and a possible association between the dermatoglyphic traits of children with obesity and late pregnancy women.

Evaluating pentraxin-3 and hypersensitivity CRP expression in obese pregnancies

ObjectiveThis study was designed to evaluate the correlation between serum pentraxin-3 (PTX3)/hypersensitivity CRP (hs-CRP) expression and obesity during pregnancy and their application as inflammatory biomarkers in obese pregnant women. Materials and methodsPregnant women scheduled to experience a single-birth at our hospital between 2016 and 2017 were selected for this nested case–control study. These patients were evaluated for age and gestational age in the first trimester (11–14 weeks), had their body mass index (BMI) calculated and were subjected to an OGTT between Week 24 and 28 of pregnancy. Obese patients with normal OGTT and a BMI of ≥30 kg/m2 in the second trimester were selected as the obese group (OBE, n = 80), and non-obese pregnant women with normal OGTT with a BMI of <30 kg/m2 were selected as the control group (CON, n = 80). ELISA was used to detect the expression of PTX3 and hs-CRP. ResultsThe expression of both PTX3 and hs-CRP increased in both groups, with increasing gestational age (P < 0.05). However, hs-CRP level in Group OBE was increased, compared to that in the healthy control (P < 0.01), during the second trimester. PTX3 expression was also significantly higher in OBE samples than in the control (P < 0.05), during the third trimester; correlation analysis demonstrated that PTX3 was positively correlated with hs-CRP, BMI, fasting plasma glucose and HOMA-IR. ConclusionsThe expression levels of both PTX3 and hs-CRP increased with increasing gestational age, and PTX3 expression was related to BMI, which serves to confirm the inflammatory response in these patients.

Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial

BackgroundThe ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model.Methods/designA multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited.DiscussionTo date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods.Trial registration numberChiCTR, ChiCTR1900026963. Registered 27 October 2019.

Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.

Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p < 0.05), exaggerated adipocyte hyperplasia (p < 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (p < 0.05) and the mRNA expression of F4/80 (p < 0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.

Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy

Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.

Longitudinal Metabolic Profiling of Maternal Obesity, Gestational Diabetes, and Hypertensive Pregnancy Disorders.

ContextComprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden.ObjectiveTo assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders.Design, Setting and ParticipantsA secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women.Main Outcome MeasuresWe assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation.ResultsAcross all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders.ConclusionsThis study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood.

Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure inutero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) inutero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child's behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.

Immune cell composition at the feto-maternal interface in health and disease

Abstract Objectives: We hypothesize that innate and adaptive leukocyte infiltration, function and localization within the placenta is altered in health and disease and that immune cell interactions play a crucial role in maintaining immune tolerance at the fetal-maternal interface. Methods: To evaluate the complexity and differences of the immune landscape in decidua basalis we examine tissue samples from healthy women and women who developed gestational diabetes (GDM). We use flow cytometry (18-plex), fluorescent multiplex immunohistochemistry and gene expression analysis. Results: Preliminary data suggest abundant innate immune cell infiltration (macrophages and neutrophils) as well as accumulation of T-cell and NK cell subsets at the fetal-maternal interface. In gestational diabetes mellitus pregnancies, we were able to observe lower T cell infiltration when compared to healthy, which was not seen in obese pregnant women. However, in both groups (obese and GDM) there was a trend for lower T regulatory cell infiltration. For monocyte and macrophage populations a trend towards lower immune cell infiltration was observed in both obese and GDM pregnancies when compared to healthy. 70–80% of macrophages show M2 polarization, which suggest that they have an important role in anti-inflammatory processes during pregnancies. We could observe also abundant neutrophil infiltration (up to 20% of all leukocytes), although there was no difference between heathy and diseased pregnancies. Conclusion: Our study comprehends a detailed picture of the immune landscape at the fetal-maternal interface in normal and GMD pregnancies, which will aid our understanding of possible dysfunctional immune mechanisms.

MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies

Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.

Breast cancer and gynecologic risks in lesbian and bisexual women.

Lesbian and bisexual women may be at an increased risk for gynecologic infections and breast cancer due to a higher prevalence of factors such as obesity, smoking, and lower pregnancy rates. This article discusses the role of healthcare professionals in preventive screening for breast and gynecologic cancers and promoting healthy living in these patients by avoiding smoking, maintaining an ideal body weight, and limiting alcohol consumption.

Growth-differentiation-factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function.

Growth-differentiation-factor 15 (GDF15) has been suggested to improve or protect beta cell function. During pregnancy, beta cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta cell function by homeostatic model assessment (HOMA). The cohort participants were 38 NW (BMI 22.3±1.7) and 35 OB (BMI 35.8±4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12 and 18months postpartum. Fasting glucose, insulin and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined. GDF15 levels increased significantly each trimester and were ~200-fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB during pregnancy, but was reversed after pregnancy with a significant interaction effect. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 was associated with lower incidence of nausea and with carrying a male foetus. The pregnancy induced increase in GDF15 associated with increased HOMA-B in OB and with reduced fasting glucose in all women. Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance.

Protective effect of Elateriospermum tapos in maternal obesity-induced deficit cognitive function of the offspring.

Pre-pregnancy obesity is a serious epidemics concern that negatively affects the neurodevelopmental of the offspring. Elateriospermum tapos (E. tapos) commonly used to enhance weight loss in obesity treatment. This study was aimed to investigate the influence of E.tapos supplement in obese maternal prior pregnancy on the offspring's bodyweight, lipid metabolism and memory function. Thirty female Sprague Dawley rats were used. Six rats were assigned to the normal diet group (DND). The remaining rats were fed with a high-fat and cafeteria diet (HFCD) to generate obesity for 5weeks. Obese rats were further divided into four groups: Negative Control (DNC; HFCD), Positive Control (DPC; Orlistat 200mg/kg), treatment 1 (DTX1; E.tapos seed 200mg/kg) and treatment 2 (DTX2, E.tapos shell 200mg/kg) were given daily, for 6weeks prior to mating. At weaning, offspring of both genders were designated into six groups according to their dam's group (n=6/group). All groups were fed with a cafeteria diet except for the control group. Memory tasks for object and place recognition were conducted on offspring at eighth weeks of age. The offspring were cull at the 12th week of age for their blood sample. Both offspring genders from DTX2 significantly reduce bodyweight, calorie intake and triglyceride level. In memory tasks, offspring from DTX2 showed a significant increase in exploration rate in place test as compared to offspring from the DNC group. This study highlights E.tapos shell as an anti-obesity agent and protecting memory deficit in obese dam's offspring.

897 Maternal obesity and male offspring sex are associated with altered hofbauer cells

Placental Hofbauer cells (HC) are resident tissue macrophages of fetal origin that play an important role in placental function and fetal immune protection and vulnerability. Maternal infections and metabolic challenges can alter the number and/or activation state of HCs. Associations between HCs and maternal and fetal characteristics remain unclear. We sought to quantify HC density and activation state to determine whether these characteristics were associated with maternal obesity and fetal sex. This is a cross-sectional study of 27 women undergoing planned cesarean delivery at term; women with hypertension or diabetes were excluded. Maternal first trimester body mass index (BMI) and fetal sex were obtained by chart review. Immunohistochemistry was performed on serial placental sections for CD163 (M2 macrophage marker) and CD68 (M1 marker, expressed by only a subset of HCs). Numbers of CD163+ and CD68+ cells per mm2 of villous area were quantified in terminal villi using ImageJ software. Quantification was performed on ten 20x images per section. Relationships between maternal obesity, fetal sex, and HC density were determined using 2-way ANOVA, with Tukey’s post hoc test to determine source of differences. 41% of patients were obese (BMI ≥ 30 kg/m2 in first trimester) and 44% had male newborns. Mean density of CD163+ HCs was greater than CD68+ HCs (mean±SD: 374±79 vs 310±64 cells/mm2, t-test, P=0.002). CD163+ HC density varied significantly by maternal obesity and fetal sex (2-way ANOVA, sex/obesity interaction P=0.04). CD163+ HC density was significantly greater in obese pregnancy, and this difference was driven disproportionately by male offspring (P=0.02, 1A). While number of CD68+ HCs did not vary by maternal obesity or fetal sex (1B), the ratio of CD163/CD68 HCs did vary significantly by fetal sex (1C, P=0.02). Maternal obesity is associated with a significant increase in CD163+ HCs, with males primarily driving this difference. Increased CD163:CD68 ratio may indicate a switch to M2 HC phenotype in males in response to maternal obesity.

Maternal obesity increases the risk of fetal cardiac dysfunction via visceral adipose tissue derived exosomes

IntroductionThere is a strong association between gestational obesity and fetal cardiac dysfunction, while the exact mechanisms remain largely unknown. The purpose of this study was to investigate the role of exosomes from maternal visceral adipose tissue in abnormal embryonic development in obese pregnancy. MethodsFemale C57BL/6J obese mice were induced by a high-fat diet (containing 60% fat). Fetal cardiac function and morphology were examined by echocardiography and histology. The placenta was extracted for histological examination. miRNA expression in exosomes from the visceral adipose tissue was profiled by RNA-seq. Gene expression of inflammatory factors was analyzed by qPCR. ResultsIn the obese pregnant mice, there were obvious inflammation and lipid droplets in the placenta. And the fetal cardiac function in obese pregnancy was also compromised. Moreover, injection of the visceral adipose tissue exosomes from the obese mice significantly decreased the fetal cardiac function in the normal lean pregnant mice. Mechanistically, the decreased expression of miR-19b might be responsible for the enhanced inflammation in the placenta. DiscussionExosomes derived from visceral adipose tissue in obese mice contribute to fetal heart dysfunction, at least partially via affecting the function of the placenta.

Longitudinal Assessment of Relationships Between Health Behaviors and IL-6 in Overweight and Obese Pregnancy

Inflammation is a common factor in adverse pregnancy outcomes (APOs). Behavioral factors influence inflammatory markers and APOs but rarely have been investigated simultaneously in pregnancy. Our purpose was to determine how diet, physical activity, and obesity are associated with interleukin (IL)-6 in early and late pregnancy. We conducted a secondary analysis of 49 overweight/obese pregnant women. Health behavior data, including diet quality using the Dietary Inflammatory Index (DII®); physical activity (Leisure Time Physical Activity scale); body mass index (BMI); and plasma IL-6 concentrations were collected at 13-16 weeks (early pregnancy) and 34-36 weeks (late pregnancy) gestation. Multiple linear regression analyses were used to determine the amount of variance explained in early and late pregnancy IL-6 concentrations by early and late pregnancy diet, physical activity, and BMI. Early diet and early BMI were the strongest predictors of early IL-6 concentrations (R2 = 0.43; p < .001) and late IL-6 concentrations (R2 = 0.30; p < .001). Late BMI predicted late IL-6 (R2 = .11; p = .02). Change in diet over pregnancy predicted late IL-6 (R2 = 0.17; p = .03). These findings suggest that maternal diet and BMI in early pregnancy, which likely reflects prepregnancy status, may have a greater impact on inflammatory processes than factors later in pregnancy. Future work should assess if behavioral factors before pregnancy produce similar relationships to those reported here, which may clarify the timing and type of lifestyle interventions to effectively reduce APOs.