Gene expression data from splenocytes of 3 week-old offspring after maternal exposure to benzyl butyl phthalate (BBP)
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ABSTRACT:
PROVIDER: PRJNA611697 | ENA |
REPOSITORIES: ENA
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Project description:The prenatal and early postnatal period is highly sensitive to environmental exposures that may interfere with the developmental programming of the immune system leading to an altered disease risk in later life. To clarify the role of early influences in activation or exacerbation of autoimmune diseases like rheumatoid arthritis (RA) we investigated the effect of maternal exposure during the prenatal and weaning period of DBA/1 mice to the plasticizer benzyl butyl phthalate (BBP) on the development of RA in the offspring. Using a mild collagen-induced arthritis (CIA) model, maternal BBP-exposure increased both the prevalence and the severity of RA in the progeny compared to un-exposed dams. Additionally, maternal BBP exposure led to elevated serum IgG1 and IgG2a level in the offspring and increased the IFN-? and IL-17 release from collagen-re-stimulated spleen cells. Transcriptome analysis of splenoytes isolated from 3-week-old pups before RA-induction revealed considerable changes in gene expression in the offspring from BBP-exposed dams. Among them were regulator of G-protein signaling 1 (rgs1), interleukin-7 receptor (il-7r) and CXC chemokine 4 (cxcr4), all genes that have previously been described as associated with RA pathology. In summary, our results demonstrate that perinatal exposure to BBP increases the susceptibility of the offspring to RA, probably via a phthalate-induced disturbed regulation of RA-relevant genes or signalling pathways.
2020-03-11 | GSE146699 | GEO
Project description:Benzyl butyl phthalate (BBP) is a chemical softener and plasticizer commonly used in toys, food packaging, wallpaper, detergents, and shampoos. The estrogenic actions of BBP have detrimental effects on humans and animals. This study investigated the specific influence of BBP on mouse oocyte maturation using in vitro and in vivo models. The results indicated that BBP exposure disrupted spindle organization, chromosomal arrangement, and the distribution of cortical actin, and led to the failure of oocyte meiotic maturation and early embryo development. Singe-cell transcriptome analysis found that BBP exposure altered the expression levels of 588 genes, most associated with mitochondria-related oxidative stress. Further analysis demonstrated that the detrimental effects of BBP involved the disruption of mitochondrial function and oxidative stress-induced early apoptosis. Nicotinamide mononucleotide supplementation reduced the adverse effects of BBP. Collectively, these findings revealed a mechanism of BBP-induced toxicity on female reproduction, and showed that nicotinamide mononucleotide provides an effective treatment for BBP actions.
2023-08-09 | GSE215872 | GEO
Project description:Endocrine disrupting chemicals (EDCs) have been linked to various health problems including effects on reproductive health. Benzyl butyl phthalate (BBP) is a commonly used plasticizer found in many consumer products that has been shown to act as an EDC and affect human reproduction and development. However, how it might impact the germline and affect the specialized cell division program of meiosis, which results in the formation of haploid gametes (i.e. eggs and sperm), remained unclear. Here, using the nematode C. elegans, we show that BBP exposure at levels within the range of what is detected in humans, impairs accurate chromosome segregation which can result in aneuploidy. Similar to mammals, BBP exposure in C. elegans results in a non-monotonic dose response, whereby lower doses result in the strongest effects, and BBP is efficiently metabolized, underscoring the use of this model system for gaining mechanistic insights into how this EDC impacts the germline. BBP results in increased levels of DNA double-strand breaks (DSBs), activation of a DNA damage checkpoint, and altered chromosome morphology in exposed germlines. We propose that BBP exposure alters gene expression and results in increased oxidative stress, resulting in increased DSBs, thereby compromising chromosome morphology and accurate segregation.
2024-09-24 | GSE264361 | GEO
Project description:Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans
| PRJNA1102026 | ENA
Project description:Exposure to Benzyl butyl phthalate deteriorates oocyte quality by inducing oxidative stress-related apoptosis and DNA damage in mice
| PRJNA891076 | ENA
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.
2015-10-10 | E-MTAB-3951 | biostudies-arrayexpress
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
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.
2013-10-31 | GSE49244 | GEO
Project description:The effects of di-butyl phthalate exposure from medications on human sperm RNA among men
| PRJNA530536 | ENA
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.
2019-09-06 | GSE129216 | GEO