Prenatal Alcohol Exposure Contributes to Negative Pregnancy Outcomes by Altering Fetal Vascular Dynamics and Placental Transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA800795 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17771545_1.fastq.gz | Fastqsanger.gz | |||
| SRR17771545_2.fastq.gz | Fastqsanger.gz | |||
| SRR17771546_1.fastq.gz | Fastqsanger.gz | |||
| SRR17771546_2.fastq.gz | Fastqsanger.gz | |||
| SRR17771547_1.fastq.gz | Fastqsanger.gz |
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Project description:Prenatal alcohol exposure (PAE) has previously been shown to alter fetal blood flow in utero and is also associated with placental insufficiency and intrauterine growth restriction (IUGR), suggesting an underlying connection between perturbed circulation and pregnancy outcomes. Here we show that a single exposure to ethanol in pregnant mice on gestational day 10 (GD10) by gavage attenuates umbilical cord blood flow transiently during gestation, explaining the observed IUGR, specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of Tet3, which is associated with spontaneous abortion. Weighted gene co-expression network analysis (WGCNA) identified erythrocyte differentiation and homeostasis as important pathways associated with improved umbilical cord blood flow as gestation progresses. WGCNA also identified sensory perception of chemical stimulus/odorant and receptor activity as important pathways associated with cranial growth. Our data suggest that PAE perturbs the expression of placental genes relevant for placental hematopoiesis and environmental sensing, resulting in transient impairment of umbilical cord blood flow and subsequently, IUGR.
2022-08-16 | GSE195489 | GEO
Project description:BackgroundPrenatal alcohol exposure (PAE) has been shown to alter fetal blood flow in utero and is also associated with placental insufficiency and intrauterine growth restriction (IUGR), suggesting an underlying connection between perturbed circulation and pregnancy outcomes.MethodsTimed-pregnant C57/BL6NHsd mice, bred in-house, were exposed by gavage on gestational day 10 (GD10) to ethanol (3 g/kg) or purified water, as a control. Pulse-wave Doppler ultrasound measurements for umbilical arteries and ascending aorta were obtained post-gavage (GD12, GD14, GD18) on 2 fetuses/litter. RNA from the non-decidual (labyrinthine and junctional zone) portion of placentas was isolated and processed for RNA-seq and subsequent bioinformatic analyses, and the association between transcriptomic changes and fetal phenotypes assessed.ResultsExposure to ethanol in pregnant mice on GD10 attenuates umbilical cord blood flow transiently during gestation, and is associated with indices of IUGR, specifically decreased fetal weight and morphometric indices of cranial growth. Moreover, RNA-seq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of Tet3, which is associated with spontaneous abortion. Weighted gene co-expression network analysis (WGCNA) identified erythrocyte differentiation and homeostasis as important pathways associated with improved umbilical cord blood flow as gestation progresses. WGCNA also identified sensory perception of chemical stimulus/odorant and receptor activity as important pathways associated with cranial growth.ConclusionOur data suggest that PAE perturbs the expression of placental genes relevant for placental hematopoiesis and environmental sensing, resulting in transient impairment of umbilical cord blood flow and, subsequently, IUGR.
| S-EPMC9325399 | biostudies-literature
Project description:Prenatal exposure to toxic metals is associated with altered placental function and adverse health outcomes. The underlying mechanisms linking in utero toxic metal exposures with later-in-life health remain unclear, though placental inflammation is posited as a potential driver. The aim of this study was to evaluate whether in utero metals presence is associated with sex-specific changes in placental protein expression. We hypothesized that sex-specific patterns of metal-associated placental protein expression would be observed, and metals presence would be positively associated with the altered expression of inflammation-associated pathways Using samples banked from the Extremely Low Gestational Age Newborn Study (ELGAN), umbilical cord tissue samples were analyzed via ICP-MS/MS for trace elements, and placental samples underwent a global untargeted proteomics analysis via LC-MS/MS. This work highlights the linkage between prenatal metals exposure and an altered placental proteome, revealing that metals in cord tissue were associated with largely distinct differences in placental protein expression, in a sexually-dimorphic manner.
2023-10-24 | PXD041694 | Pride
Project description:Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in new-born pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.
2024-07-30 | GSE273157 | GEO
Project description:Maternal Circulating miRNAs Contribute to Negative Pregnancy Outcomes by Altering Placental Transcriptome and Fetal Vascular Dynamics
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Project description:Background: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities and so on. However, the prenatal phenotypes of 16p11.2 copy number variations (CNVs) are still not well described till now. This study aimed to provide an elaborate summary of intrauterine phenotypic features for such genomic disorders. Methods: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions after birth for all cases were followed up. Meanwhile, we made a pooled analysis on the prenatal phenotypes for the published cases carrying 16p11.2 CNVs. Results: 20 fetuses (20/20884, 0.10%) with 16p11.2 CNVs were identified: five 16p11.2 BP2-BP3 deletion, ten 16p11.2 BP4-BP5 deletion and five 16p11.2 BP4-BP5 duplication. Abnormal ultrasound findings were recorded in ten participants with 16p11.2 deletions.Various degrees of intrauterine phenotypic features, ranging from normal to abnormal, were observed. No ultrasound abnormalities were observed for all 16p11.2 duplication cases during the pregnancy period. For 16p11.2 deletions, eleven cases terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except one was lost to follow up. Conclusions: Diverse prenatal phenotypes were presented in 16p11.2 CNVs, ranging from normal to abnormal. For 16p11.2 BP4-BP5 deletion, the most common structural and non-structural abnormalities were the abnormality of the vertebral column or rib and thickened nuchal translucency, respectively. 16p11.2 BP2-BP3 deletion might be closely associated with fetal growth restriction and single umbilical artery. No representative ultrasound findings for 16p11.2 duplication were observed till now. Considering the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long term follow up after birth should be carried out for these cases. We identified 20 fetuses carrying the 16p11.2 microdeletions and microduplications using chromosomal microarray analysis. And diverse prenatal phenotypes and the critical genes involved in the deleted/duplicated regions were described in this study.
2024-04-29 | GSE265911 | GEO
Project description:Objective: Chromosomal 1q21.1 deletions and duplications are genomic disorders which are usually diagnosed postnatally. However, the genotype-phenotype correlations of 1q21.1 copy number variants (CNVs) during prenatal period are still not clear. This study aimed to provide a systematical summary of prenatal phenotypes for such genomic disorders. Methods: Twenty-six prenatal amniotic fluid samples diagnosed with 1q21.1 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed for all cases simultaneously. The pregnancy outcomes and health conditions after birth for all cases were followed up. Meanwhile, prenatal cases with 1q21.1 microdeletions or microduplications in the literature were retrospectively collected. Results: Eleven pregnancies (11/8252, 0.13%) with 1q21.1 microdeletions and fifteen (15/8252, 0.18%) with 1q21.1 microduplications were identified. Among these 1q21.1 CNVs, four cases covered thrombocytopenia-absent radius (TAR) region, sixteen cases covered 1q21.1 recurrent microdeletion/microduplication region, and six cases covered all regions mentioned above. The prenatal abnormal ultrasound findings were recorded in four participants with 1q21.1 deletions and seven participants with 1q21.1 duplications. Finally, three cases with 1q21.1 deletions and five with 1q21.1 duplications terminated their pregnancies. Conclusion: 1q21.1 microdeletions were associated with increased nuchal translucency (NT), anomalies of urinary system and cardiovascular abnormalities, and 1q21.1 microduplications were correlated with cardiovascular malformations, nasal bone dysplasia and increased NT in prenatal setting. In addition, cerebral ventriculomegaly might be correlated with 1q21.1 microduplications. Considering the variable expressivity and incomplete penetrance of 1q21.1 CNVs, long term follow up after birth should be carried out for these cases. We identified 26 fetuses carrying the 1q21.1 microdeletions and microduplications using chromosomal microarray analysis. And diverse prenatal phenotypes and the critical genes involved in the deleted/duplicated regions were described in this study.
2023-08-14 | GSE240611 | GEO
Project description:Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.
2023-09-01 | GSE241836 | GEO
Project description:Prenatal adversity or stress can have long-term consequences on developmental trajec-tories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional impli-cations. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early devel-opment. As these insults can have sex-specific effects on biological outcomes, we analyzed epige-nome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cogni-tion, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may re-flect the sex-specific effects of prenatal insults on long-term functional and health outcomes and may have important implications for understanding possible mechanisms underlying fetal alco-hol spectrum disorder and other neurodevelopmental disorders.
2021-11-01 | GSE186840 | GEO
Project description:Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function
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