Fetal metabolomic signature of exposure to iAs during pregnancy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Environmental Exposure
PROVIDER: ST000051 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:BackgroundLithium is an effective treatment in pregnancy and postpartum for the prevention of relapse in bipolar disorder, but there is a lack of knowledge about the potential adverse impact on fetal development.AimsTo investigate the impact of lithium exposure on early fetal growth.MethodsIn this retrospective observational cohort study, we included all singleton pregnancies of women using lithium and referred for advanced fetal ultrasound scanning between 1994 and 2018 to the University Medical Centers in Leiden and Rotterdam, the Netherlands (n=119). The Generation R study, a population-based cohort, served as a non-exposed control population from the same geographic region (n=8184). Fetal head circumference, abdominal circumference, femur length, and transcerebellar diameter were measured by ultrasound at 18-22 weeks of gestation.ResultsLithium use during pregnancy was associated with an average increase in head circumference of 1.77 mm (95% confidence interval: 0.53, 3.01), in abdominal circumference of 5.54 mm (95% confidence interval: 3.95, 7.12) and in femur length of 0.59 mm (95% confidence interval: 0.22, 0.96) at 18-22 weeks gestation. Furthermore, lithium use during pregnancy was associated with an average increase in birth weight of 142.43 grams (95% confidence interval: 58.01, 226.89), whereas it was associated with an average decrease of 1.41 weeks in gestational duration (95% confidence interval: -1.78, -1.05).ConclusionsLithium use during pregnancy was associated with increased fetal growth parameters at 18-22 weeks gestational age and increased birth weight. Further research is needed to evaluate both short- and long-term implications, as well as the mechanisms driving this difference in growth.
| S-EPMC7859661 | biostudies-literature
Project description:Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures. To gain a deeper inside into the biochemical mechanism of such a multifactorial disease, we adopted targeted metabolomics approaches for the determination of many serum metabolites in 12 pregnant women affected by MuS by mass spectrometry analysis. Our data show a characteristic hormonal fluctuation for estrogens and progesterone, as expected. They also highlight other interesting hormonal alterations for cortisol, corticosterone, 11-deoxycortisol, 4-androstene-3,17-dione, testosterone, and 17α-hydroxyprogesterone. Furthermore, a negative correlation with progesterone levels was observed for amino acids and for acylcarnitines, while an imbalance of different sphingolipids pathways was found during pregnancy. In conclusion, these data are in agreement with the characteristic clinical signs of MuS patients during pregnancy and, if confirmed, they may add an important tessera in the complex mosaic of maternal neuroprotection.
| S-EPMC6274842 | biostudies-literature
Project description: Not available
| ST000050 | MetabolomicsWorkbench
Project description:ImportancePodophyllotoxin is an antimitotic agent primarily used in the local treatment of anogenital warts. Data that enable the assessment of the fetal safety of podophyllotoxin use during pregnancy are lacking.ObjectiveTo investigate the association between local podophyllotoxin exposure during pregnancy and risk of adverse fetal outcomes.Design, setting, and participantsThis cohort study obtained individual-level pregnancy data from various nationwide registries in Denmark from the study period of January 1, 1997, through December 31, 2016, resulting in a cohort of 1 650 649 pregnancies. Pregnancies with multiple records on overlapping dates and pregnancy records with implausible or missing information on gestational age were excluded. Local podophyllotoxin-exposed pregnancies were compared with unexposed pregnancies and matched in a 1:10 ratio according to propensity scores on a wide set of baseline characteristics. Five distinct study cohorts were constructed, one for each outcome analysis. Sensitivity analyses included a comparison of podophyllotoxin-exposed pregnancies with pregnancies with podophyllotoxin use only before pregnancy onset. Data analyses were performed from April 27, 2019, to June 26, 2019.ExposuresFilled prescription for local podophyllotoxin.Main outcomes and measuresPrimary outcomes were major birth defects and spontaneous abortions. Secondary outcomes were preterm births, small-for-gestational-age (SGA) size, and stillbirths. Logistic regression was used to estimate the prevalence odds ratios (ORs) of major birth defects, preterm births, and SGA size, and Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) of spontaneous abortions and stillbirths.ResultsThis study included 9229 pregnancies (mean [SD] maternal age at pregnancy onset, 27.7 [5.2] years) for the analyses of major birth defects and 18 590 pregnancies (mean [SD] maternal age at pregnancy onset, 26.4 [6.0] years) for the analyses of spontaneous abortions. Among the podophyllotoxin-exposed pregnancies, 29 infants (3.5%) were diagnosed with major birth defects, compared with 286 (3.4%) among the unexposed pregnancies. A total of 141 podophyllotoxin-exposed pregnancies (8.3%) ended in spontaneous abortion, compared with 1626 (9.6%) among the unexposed pregnancies. No statistically significant associations were found between podophyllotoxin exposure during pregnancy and major birth defects (prevalence odds ratio [OR], 1.02 95% CI, 0.69-1.50), spontaneous abortions (HR, 0.87; 95% CI, 0.73-1.04), preterm births (prevalence OR, 1.08; 95% CI, 0.86-1.35), SGA size (prevalence OR, 1.01; 95% CI, 0.85-1.22), or stillbirths (HR, 0.58; 95% CI, 0.18-1.86). Sensitivity analyses of the primary outcomes achieved similar results.Conclusions and relevanceFindings from this study suggest that podophyllotoxin use during pregnancy may be safe, as it did not appear to be associated with an increased risk of adverse fetal outcomes. These findings may help guide clinicians, patients, and drug regulatory authorities when prescribing podophyllotoxin.
| S-EPMC6990942 | biostudies-literature
Project description:Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.
| S-EPMC5006689 | biostudies-literature
Project description:BackgroundPrior studies have examined the association between fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] and fetal growth with either limited spatial or temporal resolution.ObjectivesIn this study, we examined the association between PM2.5 exposure during pregnancy and fetal growth measures (ultrasound parameters and birth weight) in a pregnancy cohort using spatiotemporally resolved PM2.5 in Eastern Massachusetts, USA.MethodsWe used ultrasound measures of biparietal diameter (BPD), head circumference, femur length, and abdominal circumference (AC), in addition to birth weight, from 9,446 pregnancies that were delivered at the Beth Israel Deaconess Medical Center from 2011-2016. We used linear mixed-effects models to examine the associations of PM2.5 in two exposure windows (the first 16 wk of pregnancy and the cumulative exposure up until the assessment of fetal growth) with anatomic scans (ultrasound measures at<24 wk), growth scans (ultrasound measures at≥24wk), and birth weight. All models were adjusted for sociodemographic characteristics, long-term trends, and temperature.ResultsHigher PM2.5 exposure in the first 16 wk was associated with smaller fetal growth measures, where associations were particularly strong for BPD, AC, and birth weight. For example, a 5-μg/m3 increase in PM2.5 was associated with a lower mean BPD z-score of -0.19 (95% CI: -0.31, -0.06) before 24 wk, a lower mean AC z-score of -0.15 (95% CI: -0.28, -0.01) after 24 wk, and a lower mean birth weight z-score of -0.11 (95% CI: -0.20, -0.01). Analyses examining the associations with cumulative PM2.5 exposure up until the assessment of fetal growth produced attenuated associations.ConclusionsHigher gestational exposure to PM2.5 was associated with smaller fetal growth measures at levels below the current national standards. https://doi.org/10.1289/EHP9824.
| S-EPMC8734565 | biostudies-literature
Project description:Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m(3)) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored.
| S-EPMC4851989 | biostudies-literature
Project description:BackgroundThe effects of exposure to childhood trauma (CT) may be transmitted across generations; however, the time period(s) and mechanism(s) have yet to be clarified. We address the hypothesis that intergenerational transmission may begin during intrauterine life via the effect of maternal CT exposure on placental-fetal stress physiology, specifically placental corticotropin-releasing hormone (pCRH).MethodsThe study was conducted in a sociodemographically diverse cohort of 295 pregnant women. CT exposure was assessed using the Childhood Trauma Questionnaire. Placental CRH concentrations were quantified in maternal blood collected serially over the course of gestation. Linear mixed effects and Bayesian piece-wise linear models were employed to test hypothesized relationships.ResultsMaternal CT exposure (CT+) was significantly associated with pCRH production. Compared with nonexposed women, CT+ was associated with an almost 25% increase in pCRH toward the end of gestation, and the pCRH trajectory of CT+ women exhibited an approximately twofold steeper increase after the pCRH inflection point at 19 weeks gestation.ConclusionsTo the best of our knowledge, this finding represents the first report linking maternal CT exposure with placental-fetal stress physiology, thus identifying a potential novel biological pathway of intergenerational transmission that may operate as early as during intrauterine life.
| S-EPMC4777678 | biostudies-literature
Project description:BackgroundHumans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect fetal neurodevelopment. Brain-derived neurotrophic factor (BDNF) is an important factor in neurodevelopment, but its role in PFAS-induced neurotoxicity is unclear. We investigated the association between prenatal PFAS exposure and fetal BDNF level in the umbilical cord blood in a large prospective cohort.MethodsA total of 725 pregnant women who participated in the Shanghai Birth Cohort were included. 10 PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples of early pregnancy. The BDNF level was determined by ELISA. The concentration of total mercury (Hg) in the umbilical cord blood was tested by cold vapor atomic absorption spectrometry (AAS) and included as a main confounder, along with other covariates. Multiple linear regression was used to explore the associations between PFAS concentrations and BDNF level. Quantile-based g-computation was applied to explore the joint and independent effects of PFAS on BDNF level.ResultsThe mean BDNF level in the total population was 10797 (±4713) pg/ml. Male fetuses had a higher level than female fetuses (P<0.001). A significant positive association was observed between PFHxS and BDNF level after adjusting for potential confounders [β=1285 (95% CI: 453, 2118, P=0.003)]. No association was observed between other PFAS congeners and BDNF level. Results of the mixed exposure model showed that the joint effects of PFAS mixture were not associated with BDNF [β=447 (95% CI: -83, 978, P=0.10)], while the positive association with PFHxS exposure remained significant after controlling for other PFAS [β=592 (95% CI: 226, 958, P=0.002)]. The above associations were more prominent in male [β=773 (95% CI: 25, 1520, P= 0.04)] than female fetuses [β=105 (95% CI: -791, 1002, P= 0.82)] for the mixed effects.ConclusionsPrenatal exposure to PFHxS was associated with an increased BDNF level in the umbilical blood, especially in male fetuses.
| S-EPMC8204808 | biostudies-literature
Project description:Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.
| S-EPMC5482093 | biostudies-literature