Developmental exposure to chlordecone induces transgenerational effects in somatic prostate tissue which are associated with epigenetic histone trimethylation changes
نویسندگان
چکیده
Chlordecone (CD), also known as Kepone, is an organochlorine insecticide that has been used in banana crops the French West Indies. Due to long-term contamination of soils and water, population still exposed CD. Exposure CD adulthood associated with increased risk prostate cancer (PCa). We examined transgenerational effects on murine tissue. pregnant Swiss mice The prostates from directly (F1) non-exposed (F3) male progeny were analyzed. immunofluorescence, RNA-seq ChIP-seq techniques for comprehensive analyses chromatin states prostate. observed prostatic intraepithelial neoplasia phenotype (PIN) both F1 F3 generations. Transcriptomic analysis CD-derived using revealed 970 genes 218 differentially expressed. expressed datasets could be clustered accordingly common biological processes, “cell differentiation”, “developmental process”, “regulating signaling”, suggesting generations similar processes perturbed. detected several Hox upregulated; F1, expression was mainly Hoxb Hoxd, F3, Hoxa family genes. Using a larger number replicates RT-qPCR we showed implicated testosterone synthesis (Akr1b3, Cyp11a1, Cyp17a1, Srd5a1) dramatically upregulated PIN samples; Cyp19a1, converting estradiol elevated well. found dramatic increase Esr2 containing PIN. PIN-containing samples have strong self-renewal-related (Nanog, Tbx3, Sox2, Sox3, Rb1). changes liver, CD-exposed males related DNA repair, matrix collagen inflammation pathways but not adult liver. RNA transcription epigenetic changes. Specifically, global H3K4 trimethylation (H3K4me3) decrease H3K27 (H3K27me3) mice. 129 regions 240 acquired altered H3K4me3 occupancy prostate, including highest at promoters datasets. alteration overlap 73 involved proliferation regulation, Tbx2, Stat3, Stat5a, Pou2f3 homeobox Hoxa13, Hoxa9. Our data suggest developmental exposure leads evidence implication hormonal pathway self-renewal gene capacity promote
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ژورنال
عنوان ژورنال: Environment International
سال: 2021
ISSN: ['0160-4120', '1873-6750']
DOI: https://doi.org/10.1016/j.envint.2021.106472