Genotoxic alterations of cord blood cells in newborns exposed in utero to a zidovudine-based antiretroviral combination
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37748 | GEO | 2012/05/03
SECONDARY ACCESSION(S): PRJNA163075
REPOSITORIES: GEO
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Project description:Background: Zidovudine remains the cornerstone drug for prophylaxis to prevent mother-to-child HIV-1 transmission. A mild but long-lasting hematological multilineage defect is observed in children exposed in utero. Objectives: To evaluate the effects of zidovudine-based ARV combinations on newborn cord blood cells. Methods: Cord blood-derived mononuclear cells from 22 HIV-1-uninfected newborn exposed in utero to a zidovudine-based ARV combination and from 20 healthy unexposed newborn were investigated by immunophenotyping, gene expression analysis, cytogenetic studies and functional capacity testing. To evaluate the effects of zidovudine-based ARV combinations on newborn cord blood cells.
2012-05-02 | E-GEOD-37748 | biostudies-arrayexpress
Project description:Increased morbidity and fetal growth restriction are reported in uninfected children born to human immunodeficiency virus type 1 (HIV-1)–infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress, skewing the cell’s immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART) exposure on the infants’ immune metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1–exposed infants, indicating altered mitochondrial functioning. The lipid metabolism was further dysregulated with increased triglyceride species and a subsequent decrease in phospholipids in cART/HIV-1–exposed infants compared to control infants. Proinflammatory immune mediators, lysophospholipids as well as cytokines such as CXCL10 and CCL3, were increased whereas anti-inflammatory metabolites from the cytochrome P450 pathway were reduced in cART/HIV-1–exposed infants. Taken together, these data demonstrate that the fetal metabolism is impacted by maternal factors (cART and HIV-1) and skews physiological immune responses toward inflammation in the newborn infant.
2018-06-06 | MTBLS449 | MetaboLights
Project description:HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, in order to enhance GI tract immunity, we treated SIV-infected pigtail macaques with ARVs supplemented with probiotics and prebiotics or with ARVs alone. In the colon, this synbiotic treatment resulted in increased expression of genes associated with antigen presenting cells (APCs), increased frequency and functionality of APCs, enhanced reconstitution and functionality of CD4+ T-cells and reduced fibrosis of lymphoid follicles. Thus, supplementing ARV treatment with synbiotic treatment in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis. CD45+ (clone MB4-6D6) leukocytes were sorted from thawed colon samples from 4 ARV + probiotics animals and 4 ARV alone animals
2013-02-06 | E-GEOD-42232 | biostudies-arrayexpress
Project description:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used peripheral blood mononuclear cells from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139649 | GEO
Project description:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used vaginal biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139654 | GEO
Project description:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used ectocervical biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139644 | GEO
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:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used cervicovaginal biopsies from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were taken after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC or two months after discontinuation. Treatment adherence was based on plasma TDF concentrations. The samples in this series are thought to be endocervical biopsies on the basis of their gene expression. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139645 | GEO
Project description:Background: Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth. Methods: Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood (for methylation arrays) and maternal peripheral venous blood (for cotine level measurement) were collected and an epigenome-wide association study was performed using a 450K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood. Results: The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (FisherM-bM-^@M-^Ys exact test, p=0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene. Conclusions: In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease. Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood were collected and an epigenome-wide association study was performed using a 450K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.
2015-02-16 | E-GEOD-64316 | biostudies-arrayexpress
Project description:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used cryopreserved peripheral blood mononuclear cells (PBMC) from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were unpaired, with one sample per person, after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139411 | GEO