Hypoxia-induced epigenetic transgenerational miRNAs dysregulation involved in reproductive impairment of ovary

Keng Po Lai; Cherry Chi Tim Leung; Delbert Almerick T Boncan; Nathan Tam; Xiao Lin; Simon Yuan Wang; Ting Fung Chan; Rudolf Shiu Sun Wu; Richard Yuen Chong Kong

doi:10.1016/j.cbi.2022.110176

Hypoxia-induced epigenetic transgenerational miRNAs dysregulation involved in reproductive impairment of ovary

Chem Biol Interact. 2022 Nov 1:367:110176. doi: 10.1016/j.cbi.2022.110176. Epub 2022 Sep 10.

Authors

Keng Po Lai¹, Cherry Chi Tim Leung², Delbert Almerick T Boncan³, Nathan Tam², Xiao Lin⁴, Simon Yuan Wang⁵, Ting Fung Chan³, Rudolf Shiu Sun Wu⁶, Richard Yuen Chong Kong⁷

Affiliations

¹ Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, China; Department of Chemistry, The City University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Marine Pollution, The City University of Hong Kong, Hong Kong SAR, China. Electronic address: kengplai@cityu.edu.hk.
² Department of Chemistry, The City University of Hong Kong, Hong Kong SAR, China.
³ School of Life Sciences, State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁴ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, USA.
⁵ Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
⁶ State Key Laboratory of Marine Pollution, The City University of Hong Kong, Hong Kong SAR, China; Department of Science and Environmental Studies, The Education University of Hong Kong, Hong Kong SAR, China.
⁷ Department of Chemistry, The City University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Marine Pollution, The City University of Hong Kong, Hong Kong SAR, China. Electronic address: bhrkong@cityu.edu.hk.

PMID: 36096162
DOI: 10.1016/j.cbi.2022.110176

Abstract

Hypoxia is a potent endocrine disruptor that is posing serious problems to the fish reproductive systems. Our previous studies reported that hypoxia could cause a transgenerational impairment of ovarian development and interfere hatching success in F2 offspring of marine medaka fish (Oryzias melastigma) through epigenetic regulation. As part of the epigenetic regulation, we investigated the involvement of microRNAs (miRNAs) in hypoxia-induced transgenerational reproductive impairments. In the present study, we used comparative small RNA sequencing to reveal that hypoxia caused miRNA dysregulation in ovaries of F0 hypoxia group and F2 transgenerational group. We found 4 common dysregulated miRNA in the F0 and F2 generations. Furthermore, integrated miRNA-mRNA analysis, followed by gene ontology enrichment analysis on the hypoxia-dysregulated miRNA-target genes further highlighted the importance of these dysregulated miRNAs in biological processes related to reproduction. More importantly, we identified 3 miRNA-mRNA pairs (novel miRNA-525-DIAPH2, novel miRNA-525-MYOCD, and novel miRNA-525-RAI14) that might play epigenetic roles in hypoxia-induced reproductive impairment. For the first time, our findings suggested the involvement of miRNA in hypoxia-induced reproductive impairments may be inherited via a transgenerational manner.

Keywords: Hypoxia; Ovary; Transcriptome; Transgenerational; miRNA.

MeSH terms

Animals
Endocrine Disruptors* / pharmacology
Epigenesis, Genetic
Female
Hypoxia / genetics
MicroRNAs* / genetics
MicroRNAs* / pharmacology
Oryzias*
Ovary
RNA, Messenger / genetics
Reproduction / genetics

Substances

Endocrine Disruptors
MicroRNAs
RNA, Messenger