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PloS One 2024Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction...
Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction in oocytes of their adult offspring. However, these effects were reported only in fully grown oocytes, mainly in the form of abnormal mitochondrial ultrastructure. It is unknown if obesogenic (OB) diets or maternal obesity already impact the primordial and preantral follicles. Considering the long duration and dynamics of folliculogenesis, determining the stage at which oocytes are affected and the extent of the damage is crucial for optimal reproductive management of obese patients and their daughters. Potential interaction between maternal and offspring diet effects are also not described, yet pivotal in our contemporary society. Therefore, here we examined the impact of OB diets on oocyte mitochondrial ultrastructure in primordial and activated preantral follicles in offspring from diet-induced obese or lean mothers. We used an outbred Swiss mouse model to increase the pathophysiological relevance to humans. Female mice were fed control or OB diets for 7 weeks, then mated with control males. Their female offspring were fed control or OB diets after weaning for 7 weeks (2-by-2 factorial design). Adult offspring ovarian sections were examined using transmission electron microscopy. We characterised and classified unique features of oocyte mitochondrial ultrastructure in the preantral follicles. An increase in mitochondrial matrix density was the most predominant change during follicle activation in secondary follicles, a feature that is linked with a higher mitochondrial activity. Maternal obesity increased mitochondrial density already in the primordial follicles suggesting an earlier increase in bioenergetic capacity. Maternal obesity did not induce abberant ultrastructure (abnormalities and defects) in primordial or preantral follicles. In contrast, offspring OB diet increased mitochondrial abnormalities in the primordial follicles. Further investigation of the consequences of these changes on oocyte metabolic regulation and stress levels during folliculogenesis is needed.
Topics: Animals; Oocytes; Female; Ovarian Follicle; Mice; Mitochondria; Pregnancy; Obesity; Male; Obesity, Maternal; Prenatal Exposure Delayed Effects; Diet, High-Fat
PubMed: 38935642
DOI: 10.1371/journal.pone.0305912 -
JAMA Jun 2024In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists...
IMPORTANCE
In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021.
OBJECTIVE
To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective observational study of 17 489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded.
EXPOSURE
Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols.
MAIN OUTCOMES AND MEASURES
The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference.
RESULTS
Of 17 489 patients included in the analysis, 12 430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36).
CONCLUSIONS AND RELEVANCE
A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE.
PubMed: 38935391
DOI: 10.1001/jama.2024.8684 -
AJPM Focus Aug 2024Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal... (Review)
Review
INTRODUCTION
Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal environment, specifically maternal BMI, with respiratory infections in offspring. In this rapid review, the authors review the literature supporting the hypothesis that high maternal BMI during pregnancy is associated with childhood respiratory infection incidence.
METHODS
The authors employed systematic search criteria in known databases-EMBASE, EMCARE, MEDLINE, CINAHL, and PsychINFO-searching from inception to January 2023. Included were primary research studies that involved (1) human pregnancy, (2) pregravid or gestational overweight or obesity, and (3) childhood respiratory infection with or without hospitalization.
RESULTS
Only 7 population-based cohort studies met the criteria, investigating maternal BMI as an exposure and childhood respiratory infection as an outcome (age 6 months to 18 years). Therefore, the authors conducted a qualitative analysis, and outcomes were reported. The authors found that >85% of the albeit few published studies support the hypothesis that maternal BMI may have independent and profound consequences on respiratory infection risk across childhood.
DISCUSSION
This area of research needs large-scale, well-controlled studies to better understand the relationship between maternal BMI and childhood respiratory infection. Possible resources such as cohort catalogs and combined databases are discussed. These findings add to the growing evidence that early environmental factors influence lifelong respiratory health. By incorporating a life course approach to infectious disease risk, policy makers can put this research to work and target health vulnerabilities before they arise.
PubMed: 38933528
DOI: 10.1016/j.focus.2024.100234 -
Journal of Diabetes and Metabolic... Jun 2024Obesity and metabolic syndrome are global health concerns associated with development of different types of diseases and serious health threats in the long term. Their... (Review)
Review
BACKGROUND
Obesity and metabolic syndrome are global health concerns associated with development of different types of diseases and serious health threats in the long term. Their metabolic imbalance can be attributable to inherited and environmental factors. As a considerable environmental agent, heavy metals exposure can predispose individuals to diseases like obesity. This systematic review and meta-analysis aimed to evaluate the association between heavy metals exposure and the risk of obesity.
METHODS
PubMed/MEDLINE, EMBASE and Web of Science were systematically searched until December 17, 2022. Only observational studies that evaluated heavy metals exposure and obesity were included. Studies were excluded if they assessed maternal or prenatal exposure, the mixture of heavy metals and other chemicals, reported the association with overweight or other diseases, and undesirable study designs. The Joanna Briggs Institute checklist was used for quality assessment. The pooled adjusted odds ratio (aOR) and the pooled standardized mean difference (SMD) with their 95% confidence intervals (CIs) were calculated, respectively. The publication bias was evaluated using Egger's and Begg's tests.
RESULTS
Twenty studies (n = 127755), four case-control and sixteen analytical cross-sectional studies, were included. Lead exposure was significantly associated with a lower risk of obesity (aOR: 0.705, 95% CI: 0.498-0.997), while mercury (aOR: 1.458, 95% CI: 1.048-2.031) and barium (aOR: 1.439, 95% CI: 1.142-1.813) exposure increased the risk of obesity. No significant publication bias was found and the studies had a low risk of bias.
CONCLUSION
Overall, lead exposure reduced obesity risk, while mercury and barium exposure raised it. Further large-scale observational studies are recommended to determine the roles of heavy metals in obesity.Study registration ID: CRD42023394865.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01307-0.
PubMed: 38932800
DOI: 10.1007/s40200-023-01307-0 -
Nutrients Jun 2024Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as...
Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of , , , and were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.
Topics: Animals; Gastrointestinal Microbiome; Synbiotics; Female; Bifidobacterium breve; Pregnancy; Oligosaccharides; Rats; Animals, Suckling; Dietary Supplements; Maternal Nutritional Physiological Phenomena; Lactation; Immune System; Male; Animals, Newborn
PubMed: 38931246
DOI: 10.3390/nu16121890 -
Nutrients Jun 2024The maternal microbiome plays a vital role in shaping pregnancy outcomes, but there remains a substantial gap in understanding its precise relationships to maternal... (Observational Study)
Observational Study
The maternal microbiome plays a vital role in shaping pregnancy outcomes, but there remains a substantial gap in understanding its precise relationships to maternal health, particularly in relation to potential effects of body mass index (BMI) on gut microbial diversity. The aim of this observational study was to assess maternal characteristics in association with pre-pregnancy BMI and to further assess microbial diversity in association with specific maternal characteristics. Eighty-four pregnant women were recruited during their third trimester of pregnancy from various prenatal clinics across the state of Michigan. The participants completed an enrollment questionnaire including self-reported pre-pregnancy BMI; stool samples were collected to assess the fecal microbial community composition. Pre-pregnancy obesity (BMI 30+) was associated (univariably) with antibiotic use before pregnancy, ever smoked, lower education level, and being unmarried. The gut microbiota alpha diversity was significantly different for pregnant women by pre-pregnancy BMI category (normal, overweight, obese). The beta diversity was unique for the gut microbiotas of pregnant women within each BMI category, by education level, and by marital status. Multivariable models revealed that pre-pregnancy BMI, maternal education, marital status, and maternal age were associated with the microbial diversity of the gut microbiota during pregnancy. These results give new insight into the relationship between a woman's microbiome during pregnancy and their prenatal health, along with an understanding of the relationships between socioeconomic factors and microbial diversity.
Topics: Humans; Female; Pregnancy; Body Mass Index; Adult; Feces; Gastrointestinal Microbiome; Obesity; Michigan; Young Adult; Educational Status; Socioeconomic Factors; Pregnancy Trimester, Third
PubMed: 38931236
DOI: 10.3390/nu16121881 -
Nutrients Jun 2024Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven,...
Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by the dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition and was associated with a reduced abundance of in GF offspring. Further, the expression of was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of . Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, highlighting the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and the development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.
Topics: Animals; Gastrointestinal Microbiome; Female; Pregnancy; Diet, Western; Immunity, Innate; Tryptophan; Mice; Receptors, Aryl Hydrocarbon; Mice, Inbred C57BL; Interleukin-10; Prenatal Exposure Delayed Effects; Obesity, Maternal; Liver; Maternal Nutritional Physiological Phenomena; Male; Macrophages; Disease Models, Animal
PubMed: 38931163
DOI: 10.3390/nu16121808 -
Journal of Clinical Medicine Jun 2024The placenta undergoes morphological and functional adaptations to adverse exposures during pregnancy. The effects ofsuboptimal maternal body mass index (BMI), preterm...
Gestational Age, Infection, and Suboptimal Maternal Prepregnancy BMI Independently Associate with Placental Histopathology in a Cohort of Pregnancies without Major Maternal Comorbidities.
The placenta undergoes morphological and functional adaptations to adverse exposures during pregnancy. The effects ofsuboptimal maternal body mass index (BMI), preterm birth, and infection on placental histopathological phenotypes are not yet well understood, despite the association between these conditions and poor offspring outcomes. We hypothesized that suboptimal maternal prepregnancy BMI and preterm birth (with and without infection) would associate with altered placental maturity and morphometry, and that altered placental maturity would associate with poor birth outcomes. Clinical data and human placentae were collected from 96 pregnancies where mothers were underweight, normal weight, overweight, or obese, without other major complications. Placental histopathological characteristics were scored by an anatomical pathologist. Associations between maternal BMI, placental pathology (immaturity and hypermaturity), placental morphometry, and infant outcomes were investigated for term and preterm births with and without infection. : Fetal capillary volumetric proportion was decreased, whereas the villous stromal volumetric proportion was increased in placentae from preterm pregnancies with chorioamnionitis compared to preterm placentae without chorioamnionitis. At term and preterm, pregnancies with maternal overweight and obesity had a high percentage increase in proportion of immature placentae compared to normal weight. Placental maturity did not associate with infant birth outcomes. We observed placental hypermaturity and altered placental morphometry among preterm pregnancies with chorioamnionitis, suggestive of altered placental development, which may inform about pregnancies susceptible to preterm birth and infection. : Our data increase our understanding of how common metabolic exposures and preterm birth, in the absence of other comorbidities or complications, potentially contribute to poor pregnancy outcomes and developmental programming.
PubMed: 38929907
DOI: 10.3390/jcm13123378 -
Genes Jun 2024Infant consumption of human milk (HM) is associated with a reduced risk of overweight and obesity, but the reasons for this relationship are not completely understood....
Infant consumption of human milk (HM) is associated with a reduced risk of overweight and obesity, but the reasons for this relationship are not completely understood. There is emerging evidence that micro RNAs (miRNAs) regulate infant development and metabolism, but the associations between HM miRNAs and infant growth remain poorly understood. We examined the relationship between HM miRNA consumption and infant obesity in 163 mother-infant dyads to determine (1) if miRNA profiles differentiate infants with obesity, and (2) if individual miRNAs accurately predicted infant obesity status at one year of age. Infant obesity was categorized as weight-for-length (WFL) Z scores or conditional weight gain (CWG) in the 95th percentile. HM miRNA profile was associated with infant age (r = 6.4%, = 0.001), but not maternal obesity status (r = 1.5%, = 0.87) or infant weight status (WFL Z-score) at birth (r = 0.6%, = 0.4), 1 month (r = 0.5%, = 0.6), or 4 months (r = 0.8%, = 0.2). Nine HM miRNAs were associated with either 12-month CWG or 12-month WFL Z scores. Among these 9 miRNAs, miR-224-5p remained significant in a logistic regression model that accounted for additional demographic factors (estimate = -27.57, = 0.004). These findings suggest involvement of HM miRNAs and particularly miR-224-5p in infant growth, warranting further investigation. To our knowledge, this is the largest study of HM miRNAs and early-life obesity and contributes to the understanding of the relationship between HM miRNAs and infant growth.
Topics: Humans; Milk, Human; Female; MicroRNAs; Infant; Male; Adult; Infant, Newborn; Obesity; Pediatric Obesity; Breast Feeding
PubMed: 38927748
DOI: 10.3390/genes15060813 -
Biology May 2024Maternal obesity is a well-established risk factor for offspring obesity development. The relationship between maternal and offspring obesity is mediated in part by...
Maternal obesity is a well-established risk factor for offspring obesity development. The relationship between maternal and offspring obesity is mediated in part by developmental programming of offspring metabolic circuitry, including hypothalamic signaling. Dysregulated hypothalamic inflammation has also been linked to development of obesity. We utilized an established C57Bl/6J mouse model of high-fat, high-sugar diet induced maternal obesity to evaluate the effect of maternal obesity on systemic and hypothalamic TNF-α, IL-6, and IL-1β levels in neonatal and adult offspring. The offspring of dams with obesity demonstrated increased adiposity and decreased activity compared to control offspring. Maternal obesity was associated with decreased plasma TNF-α, IL-6 and IL-1β in adult female offspring and decreased plasma IL-6 in neonatal male offspring. Neonatal female offspring of obese dams had decreased TNF-α gene expression in the hypothalamus compared to control females, while neonatal and adult male offspring of obese dams had decreased IL-6 gene expression in the hypothalamus compared to control males. In summary, our results highlight important sex differences in the inflammatory phenotype of offspring exposed to maternal obesity. Sex-specific immunomodulatory mechanisms should be considered in future efforts to develop therapeutic interventions for obesity prevention and treatment.
PubMed: 38927279
DOI: 10.3390/biology13060399