Extracellular vesicles alter trophoblast function in pregnancies complicated by COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro . We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

Preconception and developmental DEHP exposure alter liver metabolism in a sex-dependent manner in adult mouse offspring.

Environmental exposure to endocrine disrupting chemicals (EDCs) during critical periods of development is associated with an increased risk of metabolic diseases, including hepatic steatosis and obesity. Di-2-ethylhexyl-phthalate (DEHP) is an EDC strongly associated with these metabolic abnormalities. DEHP developmental windows of susceptibility are unknown yet have important public health implications. The purpose of this study was to identify these windows of susceptibility and determine whether developmental DEHP exposure alters hepatic metabolism later in life. Dams were exposed to control or feed containing human exposure relevant doses of DEHP (50 µg/kg BW/d) and high dose DEHP (10 mg/kg BW/d) from preconception until weaning or only exposed to DEHP during preconception. Post-weaning, all offspring were fed a control diet throughout adulthood. Using the Metabolon Untargeted Metabolomics platform, we identified 148 significant metabolites in female adult livers that were altered by preconception-gestation-lactation DEHP exposure. We found a significant increase in the levels of acylcarnitines, diacylglycerols, sphingolipids, glutathione, purines, and pyrimidines in DEHP-exposed female livers compared to controls. These changes in fatty acid oxidation and oxidative stress-related metabolites were correlated with hepatic changes including microvesicular steatosis, hepatocyte swelling, inflammation. In contrast to females, we observed fewer metabolic alterations in male offspring, which were uniquely found in preconception-only low dose DEHP exposure group. Although we found that preconception-gestational-lactation exposure causes the most liver pathology, we surprisingly found preconception exposure linked to an abnormal liver metabolome. We also found that two doses exhibited non-monotonic DEHP-induced changes in the liver. Collectively, these findings suggest that metabolic changes in the adult liver of offspring exposed periconceptionally to DHEP depends on the timing of exposure, dose, and sex.

Wildfires and COVID-19: syndemic impact on maternal and child health.

The prevailing COVID-19 pandemic and climate change-mediated wildfires can combine to impact maternal-child health, yet this connection remains understudied. To shape policies and design interventions to mitigate the combined effects of future global catastrophes, it is vital to holistically evaluate the impact of syndemics on maternal-child health.

Identification of Novel Regulatory Regions Induced by Intrauterine Growth Restriction in Rat Islets.

Intrauterine growth restriction (IUGR) leads to the development of type 2 diabetes in adulthood, and the permanent alterations in gene expression implicate an epigenetic mechanism. Using a rat model of IUGR, we performed TrueSeq-HELP Tagging to assess the association of DNA methylation changes and gene dysregulation in islets. We identified 511 differentially methylated regions (DMRs) and 4377 significantly altered single CpG sites. Integrating the methylome and our published transcriptome data sets resulted in the identification of pathways critical for islet function. The identified DMRs were enriched with transcription factor binding motifs, such as Elk1, Etv1, Foxa1, Foxa2, Pax7, Stat3, Hnf1, and AR. In silico analysis of 3-dimensional chromosomal interactions using human pancreas and islet Hi-C data sets identified interactions between 14 highly conserved DMRs and 35 genes with significant expression changes at an early age, many of which persisted in adult islets. In adult islets, there were far more interactions between DMRs and genes with significant expression changes identified with Hi-C, and most of them were critical to islet metabolism and insulin secretion. The methylome was integrated with our published genome-wide histone modification data sets from IUGR islets, resulting in further characterization of important regulatory regions of the genome altered by IUGR containing both significant changes in DNA methylation and specific histone marks. We identified novel regulatory regions in islets after exposure to IUGR, suggesting that epigenetic changes at key transcription factor binding motifs and other gene regulatory regions may contribute to gene dysregulation and an abnormal islet phenotype in IUGR rats.

The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation.

Islet function is critical for normal glucose homeostasis. Unlike adult ß cells, fetal and neonatal islets are more proliferative and have decreased insulin secretion in response to stimuli. However, the underlying mechanisms governing functional maturity of islets have not been completely elucidated. Pancreatic islets comprise different cell types. The microenvironment of islets and interactions between these cell types are critical for ß-cell development and maturation. Thus, the study of intact islets is optimal to identify novel molecular mechanisms controlling islet functional development. Transcriptomes and genome-wide histone landscapes of H3K4me3, H3K27me3, and H3K27Ac from intact islets isolated from 2- and 10-week-old Sprague-Dawley rats were integrated to elucidate genes and pathways modulating islet development, as well as the contribution of epigenetic regulation. A total of 4489 differentially expressed genes were identified; 2289 and 2200 of them were up- and down-regulated in 10-week islets, respectively. Ingenuity Pathway Analysis revealed critical pathways regulating functional maturation of islets, including nutrient sensing, neuronal function, immune function, cell replication, and extracellular matrix. Furthermore, we identified significant changes in enrichment of H3K4me3, H3K27me3, and H3K27Ac marks, which correlated with expression changes of genes critical for islet function. These histone marks were enriched at critical transcription factor-binding motifs, such as Hoxa9, C/EBP-ß, Gata1, Foxo1, E2f1, E2f3, and Mafb. In addition, our chromatin immunoprecipitation sequencing data revealed multiple potential bivalent genes whose poised states changed with maturation. Collectively, our current study identified critical novel pathways for mature islet function and suggested a role for histone modifications in regulating islet development and maturation.

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth.

A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB.

Environmental Exposure to Endocrine Disrupting Chemicals Influences Genomic Imprinting, Growth, and Metabolism.

Genomic imprinting is an epigenetic mechanism that results in monoallelic, parent-of-origin-specific expression of a small number of genes. Imprinted genes play a crucial role in mammalian development as their dysregulation result in an increased risk of human diseases. DNA methylation, which undergoes dynamic changes early in development, is one of the epigenetic marks regulating imprinted gene expression patterns during early development. Thus, environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risk. Here, we summarize the current literature on the impacts of in utero exposure to endocrine disrupting chemicals on genomic imprinting and metabolism in humans and rodents. We evaluate how early-life environmental exposures are a potential risk factor for adult metabolic diseases. We also introduce our mouse model of phthalate exposure. Finally, we describe the potential of genomic imprinting to serve as an environmental sensor during early development and as a novel biomarker for postnatal health outcomes.

Obesity-related IL-18 Impairs T-Regulatory Cell Function and Promotes Lung Ischemia-Reperfusion Injury.

Rationale: Primary graft dysfunction (PGD) is a severe form of acute lung injury, leading to increased early morbidity and mortality after lung transplant. Obesity is a major health problem, and recipient obesity is one of the most significant risk factors for developing PGD. Objectives: We hypothesized that T-regulatory cells (Tregs) are able to dampen early ischemia-reperfusion events and thereby decrease the risk of PGD, whereas that action is impaired in obese recipients. Methods: We evaluated Tregs, T cells, and inflammatory markers, plus clinical data, in 79 lung transplant recipients and 41 liver or kidney transplant recipients and studied two groups of mice on a high-fat diet (HFD), which did ("inflammatory" HFD) or did not ("healthy" HFD) develop low-grade inflammation with decreased Treg function. Measurements and Main Results: We identified increased levels of IL-18 as a previously unrecognized mechanism that impairs Tregs' suppressive function in obese individuals. IL-18 decreases levels of FOXP3, the key Treg transcription factor, decreases FOXP3 di- and oligomerization, and increases the ubiquitination and proteasomal degradation of FOXP3. IL-18-treated Tregs or Tregs from obese mice fail to control PGD, whereas IL-18 inhibition ameliorates lung inflammation. The IL-18-driven impairment in Tregs' suppressive function before transplant was associated with an increased risk and severity of PGD in clinical lung transplant recipients. Conclusions: Obesity-related IL-18 induces Treg dysfunction that may contribute to the pathogenesis of PGD. Evaluation of Tregs' suppressive function together with evaluation of IL-18 levels may serve as a screening tool to identify obese individuals with an increased risk of PGD before transplant.

Variably methylated retrotransposons are refractory to a range of environmental perturbations.

The agouti viable yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. Avy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.

Neonatal IL-4 exposure decreases adipogenesis of male rats into adulthood.

The cytokine interleukin 4 (IL-4) can increase beige adipogenesis in adult rodents. However, neonatal animals use a distinct adipocyte precursor compartment for adipogenesis as compared with adults. In this study, we address whether IL-4 can induce persistent effects on adipose tissue when administered subcutaneously in the interscapular region during the neonatal period in Sprague-Dawley rats. We injected IL-4 into neonatal male rats during postnatal days 1-6, followed by analysis of adipose tissue and adipocyte precursors at 2 wk and 10 wk of age. Adipocyte precursors were cultured and subjected to differentiation in vitro. We found that a short and transient IL-4 exposure in neonates upregulated uncoupling protein 1 (Ucp1) mRNA expression and decreased fat cell size in subcutaneous white adipose tissue (WAT). Adipocyte precursors from mature rats that had been treated with IL-4 as neonates displayed a decrease in adiponectin (Adipoq) but no change in Ucp1 expression, as compared with controls. Thus, neonatal IL-4 induces acute beige adipogenesis and decreases adipogenic differentiation capacity long term. Overall, these findings indicate that the neonatal period is critical for adipocyte development and may influence the later onset of obesity.NEW & NOTEWORTHY We used neonatal injections in rat to show that IL-4 decreases adipogenesis and increases browning of white fat. In adulthood, adipocyte precursors show persistently decreased adipogenesis but not increased browning. These studies in the neonate are the first, to our knowledge, to show that IL-4 can have long-lasting effects.

Immune dysfunction in developmental programming of type 2 diabetes mellitus.

Intrauterine growth restriction (IUGR) is a common complication of pregnancy and increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) later in life. Alterations in the immune system are implicated in the pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is a delicate balance as it must remain tolerant of maternal antigens whilst also preparing for the post-birth environment. In addition, the fetal immune system is susceptible to an altered intrauterine milieu caused by maternal and placental inflammatory mediators or secondary to nutrient and oxygen deprivation. Pancreatic-resident macrophages populate the pancreas during fetal development, and their phenotype is dynamic through the neonatal period. Furthermore, macrophages in the islets are instrumental in islet development as they influence ß-cell proliferation and islet neogenesis. In addition, cytokines, derived from ß-cells and macrophages, are important to islet homeostasis in the fetus and adult and, when perturbed, can cause islet dysfunction. Several activated immune pathways have been identified in the islets of people who experienced IUGR, with alternations in the levels of IL-1ß and IL-4 as well as changes in TGFß signalling. Leptin levels are also altered. Immunomodulation has shown therapeutic benefit in T2DM and might be particularly useful in IUGR-induced T2DM.

Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex-specific manner.

KEY POINTS: The prevalence of obesity and non-alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible aetiology as it is thought to be more lipogenic than glucose. In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance. Multiple metabolites including lipids, bile acids, carbohydrates and amino acids were altered in liver in a sex-specific manner at 6 weeks of age. Some of these changes were also present in adulthood even though HFCS exposure ended at 6 weeks. HFCS significantly altered the gut microbiome, which was associated with changes in key microbial metabolites. These results suggest that HFCS intake during adolescence has profound metabolic changes that are linked to changes in the microbiome and these changes are sex-specific. ABSTRACT: The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20 years has been linked to increased consumption of high fructose corn syrup (HFCS), making it essential to determine the short- and long-term effects of HFCS during this vulnerable developmental window. We hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signalling pathways and alters gut microbial composition, contributing to changes in energy metabolism with sex-specific effects. C57bl/6J mice with free access to HFCS during adolescence (3-6 weeks of age) underwent glucose tolerance and body composition testing and hepatic metabolomics, gene expression and triglyceride content analysis at 6 and 30 weeks of age (n = 6-8 per sex). At 6 weeks HFCS-exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides (females) and de novo lipogenesis gene expression (ACC, DGAT, FAS, ChREBP, SCD, SREBP, CPT and PPARα) with sex-specific effects. At 30 weeks, HFCS-exposed mice also had abnormalities in glucose tolerance (males) and fat mass (females). HFCS exposure enriched carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6 weeks with changes in secondary bile metabolism at 6 and 30 weeks. Microbiome studies performed immediately before and after HFCS exposure identified profound shifts of microbial species in male mice only. In summary, short-term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which continue to be altered in adulthood, and changes the microbiome in a sex-specific manner.

Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta.

Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression and/or modulates metabolite production and abundance in the placenta. 1871 differentially expressed genes were identified in LPS-exposed placenta. Among them, 1,149 and 722 transcripts were increased and decreased, respectively. Ingenuity pathway analysis showed alterations in genes and canonical pathways critical for regulating oxidative stress, mitochondrial function, metabolisms of glucose and lipids, and vascular reactivity in LPS-exposed placenta. Many upstream regulators and master regulators important for nutrient-sensing and mitochondrial function were also altered in inflammation exposed placentae, including STAT1, HIF1α, mTOR, AMPK, and PPARα. Comprehensive quantification of metabolites demonstrated significant alterations in the glucose utilization, metabolisms of branched-chain amino acids, lipids, purine and pyrimidine, as well as carbon flow in TCA cycle in LPS-exposed placenta compared to control placenta. The transcriptome and metabolome were also integrated to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the placenta transcriptome and metabolome were identified in placentae exposed to intrauterine inflammation. Altered mitochondrial function and energy metabolism may underline the mechanisms of inflammation-induced placental dysfunction.

Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation.

Pancreatic ß-cell dysfunction and reduced insulin secretion play a key role in the pathogenesis of diabetes. Fetal and neonatal islets are functionally immature and have blunted glucose responsiveness and decreased insulin secretion in response to stimuli and are far more proliferative. However, the mechanisms underlying functional immaturity are not well understood. Pancreatic islets are composed of a mixture of different cell types, and the microenvironment of islets and interactions between these cell types are critical for ß-cell development and maturation. RNA sequencing and quantitative proteomic data from intact islets isolated from fetal (embryonic day 19) and 2-week-old Sprague-Dawley rats were integrated to compare their gene and protein expression profiles. Ingenuity Pathway Analysis (IPA) was also applied to elucidate pathways and upstream regulators modulating functional maturation of islets. By integrating transcriptome and proteomic data, 917 differentially expressed genes/proteins were identified with a false discovery rate of less than 0.05. A total of 411 and 506 of them were upregulated and downregulated in the 2-week-old islets, respectively. IPA revealed novel critical pathways associated with functional maturation of islets, such as AMPK (adenosine monophosphate-activated protein kinase) and aryl hydrocarbon receptor signaling, as well as the importance of lipid homeostasis/signaling and neuronal function. Furthermore, we also identified many proteins enriched either in fetal or 2-week-old islets related to extracellular matrix and cell communication, suggesting that these pathways play critical roles in islet maturation. Our present study identified novel pathways for mature islet function in addition to confirming previously reported mechanisms, and provided new mechanistic insights for future research on diabetes prevention and treatment.

Paternal bisphenol A exposure in mice impairs glucose tolerance in female offspring.

Humans are ubiquitously exposed bisphenol A (BPA), and epidemiological studies show a positive association between BPA exposure and diabetes risk, but the impact of parental exposure on offspring diabetes risk in humans is unknown. Our previous studies in mice show disruption of metabolic health upon maternal BPA exposure. The current study was undertaken to determine whether exposure in fathers causes adverse metabolic consequences in offspring. Male C57BL/6 J mice were exposed to BPA in the diet beginning at 5 weeks of age resulting in the following dietary exposure groups: Control (0 µg/kg/day), Lower BPA (10 µg/kg/day) and Upper BPA (10 mg/kg/day). After 12 weeks of dietary exposure, males were mated to control females. Mothers and offspring were maintained on the control diet. Post-pubertal paternal BPA exposure did not affect offspring body weight, body composition or glucose tolerance. However, when fathers were exposed to BPA during gestation and lactation, their female offspring displayed impaired glucose tolerance in the absence of compromised in vivo insulin sensitivity or reduced ex vivo glucose-stimulated insulin secretion. Male offspring exhibited normal glucose tolerance. Taken together, these studies show there is an early window of susceptibility in which paternal BPA exposure can cause sex-specific impairments in glucose homeostasis.

Maternal and neonatal response to COVID-19.

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare. Interestingly, despite lack of SARS-CoV-2 placenta infection, there are several reports of significant abnormalities in placenta morphology. Continued research on pregnant women infected with SARS-CoV-2 and their offspring is vitally important.

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats.

Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.

The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth.

The placenta is metabolically active and supports the growth of the fetus. We hypothesize that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may result in spontaneous preterm birth (SPTB). To explore this hypothesis, we performed a nested cased control study of metabolomic signatures in placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation). To control for the effects of gestational age on placenta metabolism, we also studied a subset of metabolites in non-laboring preterm and term Rhesus monkeys. Comprehensive quantification of metabolites demonstrated a significant elevation in the levels of amino acids, prostaglandins, sphingolipids, lysolipids, and acylcarnitines in SPTB placenta compared to term placenta. Additional quantification of placental acylcarnitines by tandem mass spectrometry confirmed the significant elevation in SPTB human, with no significant differences between midgestation and term placenta in Rhesus macaque. Fatty acid oxidation as measured by the flux of 3H-palmitate in SPTB placenta was lower than term. Collectively, significant and biologically relevant alterations in the placenta metabolome were identified in SPTB placenta. Altered acylcarnitine levels and fatty acid oxidation suggest that disruption in normal substrate metabolism is associated with SPTB.

The Role of Adipocyte Precursors in Development and Obesity.

Maintenance of adipocyte precursors is critical for regulating metabolism and preventing obesity related disease. These precursors have been immortalized and studied in cellular models as well as-more recently-in animal models. However, little is known about adipocyte precursors from animals of different ages. Most research has focused on adipocyte precursors during obesity. This review goes over the most recent reports of adipocyte precursors during development and in adulthood. Some of these new analyses are due to new techniques such as single cell-RNA sequencing and temporally controlled lineage tracing. With these tools, we have been able to further our understanding of adipocyte precursor lineages and their different regulatory mechanisms. As we learn more about adipocyte precursor plasticity and regulation, we can hope to use this knowledge for future clinical applications.