The effects of di-butyl phthalate exposure from medications on human sperm RNA among men
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA530536 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8836360.fastq.gz | Fastqsanger.gz | |||
| SRR8836370.fastq.gz | Fastqsanger.gz | |||
| SRR8836380.fastq.gz | Fastqsanger.gz | |||
| SRR8836390.fastq.gz | Fastqsanger.gz | |||
| SRR8836400.fastq.gz | Fastqsanger.gz |
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Project description:The data comes from a study, where three-spined sticklebacks (Gasterosteus aculeatus) were exposed to di-n-butyl phthalate (DBP) and 17α ethinyl-oestradiol (EE2) at nominal concentrations 35 μg/L and 40 ng/L, respectively, for four days. The aim of the study was to obtain insight into the acute transcriptional responses putatively associated with endocrine disruption. RNA samples from the testes of eight individuals fish per treatment (including solvent controls, exposed only to DMSO) were used in the microarray analysis, covering the expression of approximately 21000 genes.
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Project description:Endocrine disruptors, such as phthalates, are suspected of affecting reproductive function. The Mesalamine and Reproductive Health Study (MARS) was designed to address the physiological effect of in-vivo phthalate exposure on male reproduction in patients with Inflammatory Bowel Disease (IBD). As part of this effort, sperm RNA profiles as an effect of exposure to DBP were longitudinally assessed using a cross-over cross-back design of binary, high or background, levels of DBP. As the DBP level was altered, numerous sperm RNA elements were differentially expressed, and suggest that exposure to or removal from high DBP produces effects that require longer than one spermatogenic cycle to resolve. In comparison, small RNAs are minimally affected by DBP exposure. While initial study medication (high or background) implicates different biological pathways, initiation on the high-DBP condition activated oxidative stress and DNA damage pathways. Using ejaculated sperm, this work provides insight into the male germline’s response to phthalate exposure.
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Project description:Phthalates are ubiquitous pollutants in the environment; however, the mechanisms of phthalate-associated reproductive disorders in men are not fully understood. The aim of this study is to investigate associations between urinary phthalate metabolite concentrations and sperm DNA methylation. The study was conducted on 697 men from three prospective pregnancy cohorts: Longitudinal Investigation of Fertility and the Environment (LIFE) Study, Sperm Environmental Epigenetics and Development Study (SEEDS), and Environment and Reproductive Health (EARTH) Study.
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Project description:The goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints. Three paired analyses were performed using the LIMMA package in R (commands lmfit and eBayes), with the Benjamini-Hochberg correction for multiple comparisons (Smyth 2005): vehicle-treated xenografts vs. unimplanted testis (n=5), abiraterone-treated xenografts vs. matched control xenografts (n=3), and DBP-treated xenografts vs. matched control xenografts (n=3). There were significant differences in gene expression between grafted and ungrafted samples, including dramatic upregulation of microRNAs. Gene expression analysis also showed that abiraterone decreased expression of genes related to cell differentiation, while DBP induced expression of oxidative stress response genes and decreased expression of factors related to embryonic development. 17 xenograft samples were analyzed, including 5 unimplanted samples, 6 vehicle treated xenografts, 3 abiraterone acetate-treated xenografts, and 3 DBP-treated xenografts. Samples were paired (derived from the same donor tissue) for each comparison: vehicle vs. unimplanted (n=5), abiraterone vs. vehicle (n=3), and DBP vs. vehicle (n=3).
2013-10-31 | E-GEOD-49244 | biostudies-arrayexpress
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Project description:To answer the question of whether preconception phthalate and phthalate replacements associated with sperm differentially methylated regions (DMRs) among men undergoing in-vitro fertilization, genome-wide DNA-methylation profiles of 48 human sperm samples were generated by bisulfite-based Illumina 450K BeadChip arrays. The sperm DNA methylation is then correlated with urinary phthalate metabolite concentrations.
2017-10-01 | GSE102970 | GEO
Project description:Endocrine disruptors, such as phthalates, are suspected of affecting reproductive function. The Mesalamine and Reproductive Health Study (MARS) was designed to address the physiological effect of in vivo phthalate exposure on male reproduction in patients with Inflammatory Bowel Disease (IBD). As part of this effort, the effect on sperm RNAs to DBP exposure were longitudinally assessed using a cross-over cross-back binary design of high or background, exposures to DBP. As the DBP level was altered, numerous sperm RNA elements (REs) were differentially expressed, suggesting that exposure to or removal from high DBP produces effects that require longer than one spermatogenic cycle to resolve. In comparison, small RNAs were minimally affected by DBP exposure. While initial study medication (high or background) implicates different biological pathways, initiation on the high-DBP condition activated oxidative stress and DNA damage pathways. The negative correlation of REs with specific genomic repeats suggests a regulatory role. Using ejaculated sperm, this work provides insight into the male germline's response to phthalate exposure.
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Project description:Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011-2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR7-phthalates: 1.56 and WQS OR8-phthalates: 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.
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