Prolonged exposure of azocyclotin induced inter- and transgenerational endocrine disruption on Danio rerio linked to transcriptomic and DNA methylomic alterations. (September 2022)

• Record Type: Journal Article
• Authors: Jiao, Fang; Ma, Yongfang; Hu, Tiantian; Qiao, Kun; Jiang, Yao; Zhu, Wei; Jin, Quan; Gui, Wenjun
• Is Part Of: Chemosphere. Volume 302(2022)
• Publication Date: 2022-09
• Subjects: Azocyclotin -- Zebrafish -- Transgenerational endocrine disruption -- Transcriptomic -- DNA methylation; ACT azocyclotin -- BW body weight -- CAO cortical alveolar oocyte -- DEG differentially expressed gene -- DMC differentially methylated cytosine -- DMG differentially methylated gene -- DMR differentially methylated region -- DMSO dimethyl sulfoxide -- dpf days post fertilization -- EC20 effect concentration 20% -- EEDCs environmental endocrine disrupting compounds -- EVO early vitellogenic oocyte -- FR fertilization rate -- GSI gonadosomatic index -- HB heart beat -- hpf hours post fertilization -- HPG hypothalamus-pituitary- gonad -- HPT hypothalamus-pituitary-thyroid -- HR hatching rate -- HSI hepatosomatic index -- LO late oocyte -- LOD detection of limit -- LOEC lowest-observed-effect-concentration -- MR malformation rate -- MS-222 tricaine methanesulfonate -- NOEC no-observed-effect-concentration -- OTCs organotin compounds -- PCR polymerase chain reaction -- PO primary oocyte -- Sc spermatocyte -- Sg Spermatogonia -- SMF spontaneous movement frequency -- SR survival rate -- Sz spermatozoa -- UPLC-MS/MS ultra-performance liquid chromatography-tandem mass spectrometry -- VC vehicle control -- WBL whole body length -- WGB-Seq whole genome bisulfite sequencing; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.134847
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: The transgenerational effect assessment linked to epigenetic analysis of environmental pollutants on eco (toxico)logical relevant species is regarded as a potential future risk-assessment tool. As an organotin acaricide widely used in China, azocyclotin can lead to endocrine disrupting effect on directly exposed environmental organisms, but whether it has transgenerational negative impact remains unknown. In order to illustrate this issue, in the present study, zebrafish, an aquatic model animal, was exposed to azocyclotin at less than μg/L level in a time span of embryonic stage to adult stage. Subsequently, the developmental and reproductive endocrine disrupting effects of azocyclotin on exposed F0 and unexposed offspring (F1 and F2) were evaluated. Result indicated that parentally exposed to 0.36 μg/L azocyclotin induced embryonic toxicity to unexposed offspring, and significantly ( p < 0.05) reduced body weight (by 8.5%–13.9%), whole body length (by 4.8%–14.3%), hepatosomatic index (by 15.6%–24.3%), gonadosomatic index (by 5.3%–17.1%), egg production (by 19.5%–25.4%), estradiol content (47.0%–65.0%) and proportion of mature germ cells (by 29.3%–41.0% and 39.2%–47.7% for late oocytes and spermatozoa, respectively) in adults of F0 and offspring. Additionally, azocyclotin decreased the contents of 5-methycytosine in gonads of unexposed offspring (by 9.9%–38.6%, p < 0.05), led to genome-wide gene up-regulated expression bias and genomic DNA hypomethylation tendency in unexposed offspring. Moreover, based on the level of differentially methylated cytosine in promoter regions/gene body regions, it was found totally 5331/11, 170 (in F1) and 3808/7507 (in F2) differentially expressed genes were closely related with differentially methylated genes (r > 0.6). The present study provided a primary evidence that prolonged exposure to low dose azocyclotin induced inter- and transgenerational endocrine disrupting effects on zebrafish probably linked to transcriptomic and DNA methylomic alterations. Graphical abstract: Image 1 Highlights: ACT led to developmental and reproductive toxicity to F0 adult zebrafish. Parentally exposed to ACT led to endocrine disrupting effect on unexposed offspring. ACT changed genome-wide gene expression profiles of unexposed offspring embryos. ACT led to global DNA hypomethylation in exposed F0 and unexposed offspring. ACT induced transgenerational epigenetic effect via DNA methylation change.