Transcriptomic analysis of the seminal vesicle response to the reproductive toxicant acrylamide
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ABSTRACT:
PROVIDER: PRJNA761430 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15746453.fastq.gz | Fastqsanger.gz | |||
| SRR15746455.fastq.gz | Fastqsanger.gz | |||
| SRR15746457.fastq.gz | Fastqsanger.gz | |||
| SRR15746459.fastq.gz | Fastqsanger.gz | |||
| SRR15746461.fastq.gz | Fastqsanger.gz |
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Project description:The seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developmental programming of offspring phenotype. Despite the significance of the seminal vesicles in reproduction, their biology remains poorly defined. Here, to advance understanding of seminal vesicle biology, we analyse the mouse seminal vesicle transcriptome under normal physiological conditions and in response to acute exposure to the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or vehicle control daily for five consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection.
2021-09-14 | GSE183632 | GEO
Project description:The seminal vesicles are an integral part of the male accessory gland system, and are responsible for producing a complex array of bioactive moieties that support gamete function and promote reproductive success. However, despite their physiological significance, the biology of the seminal vesicles remains poorly defined. Here, we exploit an established reproductive toxicant model, where mice were administered acrylamide (25 mg/kg bw/day) or control each morning for 5 consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection, to complete the first proteomic assessment of mouse seminal vesicles. A total of 5,013 proteins were identified in the core seminal vesicle proteome with bioinformatics analysis of identifying cell proliferation, transcript/protein production and cellular death and survival pathways as prominent biological processes. Comparison of our acrylamide to control seminal vesicle proteome revealed 311 differentially regulated (-1.5 ≤ FC ≥ 1.5, p ≤ 0.05, 205 up-regulated, 106 down-regulated) proteins with immunoblotting analysis confirming proteomic data. Pathways that initiate protein synthesis to promote cellular survival were prominent amongst the dysregulated cellular pathways and RICTOR (Z-score = -3.64, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as a contributor to protein changes with acrylamide leading to a significant increase in 8-OHdG in epithelial cells (5-fold increase, p = 0.016). Direct effects of acrylamide on seminal vesicle function were observed through a reduction in seminal vesicle secretion weight and overall protein content. Together these finding support the emerging concept that in addition to sperm, paternal exposures exert significant influence on the seminal vesicles, and identify new pathways to develop targeted interventions with which to manipulate fertility and reproductive outcomes.
2021-05-31 | PXD021998 | Pride
Project description:During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. The majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report a single-cell RNA-Seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory epithelial cells in this tissue, identifying a relative homogeneous population of the epithelial cells responsible for producing the majority of seminal fluid. We also define the immune cell populations – including large populations of macrophages, dendritic cells, T cells, and NKT cells – which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.
2024-05-16 | GSE267191 | GEO
Project description:Paternal exposure to a range of environmental and lifestyle factors elicits distinct changes to the sperm sncRNA profile; modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures effect the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the potent reproductive toxicant, acrylamide. Further, we traced the differential accumulation of acrylamide responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identified extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development. These data provide a causative mechanistic link to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos
2021-10-07 | PXD022865 | Pride
Project description:BackgroundThe seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developmental programming of offspring phenotype. Despite the significance of the seminal vesicles in reproduction, their biology remains poorly defined. Here, to advance understanding of seminal vesicle biology, we analyse the mouse seminal vesicle transcriptome under normal physiological conditions and in response to acute exposure to the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or vehicle control daily for five consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection.ResultsA total of 15,304 genes were identified in the seminal vesicles with those encoding secreted proteins amongst the most abundant. In addition to reproductive hormone pathways, functional annotation of the seminal vesicle transcriptome identified cell proliferation, protein synthesis, and cellular death and survival pathways as prominent biological processes. Administration of acrylamide elicited 70 differentially regulated (fold-change ≥1.5 or ≤ 0.67) genes, several of which were orthogonally validated using quantitative PCR. Pathways that initiate gene and protein synthesis to promote cellular survival were prominent amongst the dysregulated pathways. Inflammation was also a key transcriptomic response to acrylamide, with the cytokine, Colony stimulating factor 2 (Csf2) identified as a top-ranked upstream driver and inflammatory mediator associated with recovery of homeostasis. Early growth response (Egr1), C-C motif chemokine ligand 8 (Ccl8), and Collagen, type V, alpha 1 (Col5a1) were also identified amongst the dysregulated genes. Additionally, acrylamide treatment led to subtle changes in the expression of genes that encode proteins secreted by the seminal vesicle, including the complement regulator, Complement factor b (Cfb).ConclusionsThese data add to emerging evidence demonstrating that the seminal vesicles, like other male reproductive tract tissues, are sensitive to environmental insults, and respond in a manner with potential to exert impact on fetal development and later offspring health.
| S-EPMC8499523 | biostudies-literature
Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used for expression profiling of 11 normal prostate and 7 seminal vesicle specimens (6 of which were matched pairs), against a universal RNA reference. Extracted expression ratios were normalized by array then mean centered by gene, and expression differences between normal prostate and seminal vesicle identified using Significance Analysis of Microarrays (SAM).
2008-05-08 | E-GEOD-11376 | biostudies-arrayexpress
Project description:Acrylamide is a reproductive toxicant that has been detected in foods such as potato chips and breads. The consequences of chronic exposure to acrylamide in the human diet are unknown; however we previously reported that exposure to acrylamide at levels equivalent to human exposure produced high levels of genetic damage in early male germ cells of mice [Nixon et al. ToxSci 129(1), 135–145 (2012)]. In the present study, we examined changes in testicular gene expression in these mice to examine the potential mechanisms involved in acrylamide induced DNA damage in male germ cells and to provide a better understanding of the reproductive toxic effects of acrylamide in the male.
2014-06-01 | GSE47574 | GEO
Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set
2008-05-08 | GSE11376 | GEO
Project description:Acrylamide is a reproductive toxicant that has been detected in foods such as potato chips and breads. The consequences of chronic exposure to acrylamide in the human diet are unknown; however we previously reported that exposure to acrylamide at levels equivalent to human exposure produced high levels of genetic damage in early male germ cells of mice [Nixon et al. ToxSci 129(1), 135–145 (2012)]. In the present study, we examined changes in testicular gene expression in these mice to examine the potential mechanisms involved in acrylamide induced DNA damage in male germ cells and to provide a better understanding of the reproductive toxic effects of acrylamide in the male. Adult male mice were subjected to chronic acrylamide exposure via the drinking water at concentrations of 0, 0.001, 0.01, 0.1, 1 and 10 µg/ml for 1, 6 and 12 months. The testes were collected at each time point for RNA extraction and hybridization on an Illumina Sentrix Mouse ref-8 v2 Beadchip.
2014-06-01 | E-GEOD-47574 | biostudies-arrayexpress
Project description:The seminal vesicles are male accessory sex glands that contribute the bulk of the seminal plasma in which mammalian spermatozoa are bathed during ejaculation. In addition to helping convey sperm through the ejaculatory duct, seminal vesicle secretions support sperm survival after ejaculation and influence the female reproductive tract to promote receptivity to pregnancy. Despite its biological importance, there is limited understanding of seminal vesicle fluid (SVF) composition with only 75 proteins having been identified in publicly available proteomic analyses. To address this limitation, here we report new preparative methodology involving sequential solubilization of mouse SVF in guanidine hydrochloride, prior to acetone precipitation and analysis by label-free quantitative mass spectrometry. This strategy identified 126 proteins, including 83 previously undetected in SVF. Members of the seminal vesicle secretory protein family were the most abundant, accounting for 79% of all peptide spectrum matches. Functional analysis of SVF proteins identified inflammation and formation of the vaginal plug as the two most prominent biological processes. Notable additional processes included modulation of sperm function and regulation of the female reproductive tract immune environment. Together, these findings provide a robust methodological framework for future SVF studies and identify novel proteins with the potential to influence both male and female reproductive health.
2022-01-20 | PXD028564 | Pride