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Environmental stress such as nutrient deprivation across multiple fields in nature causes physiological and biochemical changes in organism. Understanding the potential epigenetic modulations to phenotypic variation upon nutrient deprivation stress is crucial for environmental assessments. Here, the methyl-cytosine at single-base resolution was mapped across the whole genome and the methylation patterns and methylation levels coordinated with transcript analysis were systemically elaborated in zebrafish embryonic fibroblast cells under serum starvation stress. The down-regulated genes mainly annotated to the pathways of DNA replication and cell cycle that were consistent with cell physiological changes. Vast differentially methylated regions were identified in genomic chromosome and showed enrichment in the intron and intergenic regions. In an integrated transcriptome and DNA methylation analyses, 135 negatively correlated genes were determined, wherein the hub genes of gins2, cdca5, fbxo5, slc29a2, suv39h1b, and zgc:174160 were predominant responsive to the nutrient condition changes. Besides, nutrient recovery and DNA methyltransferases inhibitor supplements partly rescued cell proliferation with decrease of DNA methylation and reactivation of several depressed genes, implying the possible intrinsic relationships among cell physiological state, mRNA expression, and DNA methylation. Collectively, current study proved the broad role of DNA methylation in governing cellular responses to nutrient deprivation and revealed the epigenetic risk of starvation stress in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The starvation is a common and severe stress for animal survival and development. In aquatic environment, many fish suffer starvation stress in different extent because of the natural migration or feed limitation. When subjected to starved conditions, organisms will employ various adaptive physiological, biochemical, and behavioral changes to regulate metabolism and maintain homeostasis. In the present study, adult female zebrafish were deprived of feed for 1 to 3 weeks to detect the starved effects on adults and larvae. The results showed that biological indexes, RNA/DNA ratios, and nutritional indexes significantly decreased in the female fish after starvation. The number of mature follicles reduced while the average spawning diameter of oocytes increased. For the larvae, the maternal starvation stress distinctly delayed embryonic hatching, decreased larval body length, disrupted larval swimming ability, and reduced survival rate at early-life stages. Furthermore, we found that DNA methylation might conduce to the downregulated mRNA expression of anti-Müllerian hormone and cytochrome P450 aromatase in retarded ovaries under starved conditions. Significant effects on autophagic transcription were shown in maternal ovary and larvae responded to starvation stress. Taken together, our study systematically revealed the reproductive impairments of starvation stress and would facilitate the investigation of environmental stress in teleost fish. Unlabelled Image • Starvation affected biological indexes and nutritional indexes of female zebrafish. • Starvation reduced ovarian fecundity and disturbed oogenesis in zebrafish. • Maternal starvation impaired the development and fitness of larvae at early-life stages. • The mRNA expression of amh , cyp19a1a , and autophagic genes responded to starvation stress in zebrafish. [ABSTRACT FROM AUTHOR]