Overexpression and Knockdown of Hypoxia-Inducible Factor 1 Disrupt the Expression of Steroidogenic Enzyme Genes and Early Embryonic Development in Zebrafish

Hypoxia is an important environmental stressor leading to endocrine disruption and reproductive impairment in fish. Although the hypoxia-inducible factor 1 (HIF-1) is known to regulate the transcription of various genes mediating oxygen homeostasis, its role in modulating steroidogenesis-related gen...

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Bibliographic Details
Published in:Gene Regulation and Systems Biology 2017-06, Vol.2017 (11), p.1177625017713193-1177625017713193
Main Authors: Tan, Tianfeng, Yu, Richard Man Kit, Wu, Rudolf Shiu Sun, Kong, Richard Yuen Chong
Format: Article
Language:English
Subjects:
Aldosterone synthase
Anoxia
Authorship
Cholesterol
Cytochrome
Danio rerio
Dehydrogenases
Embryogenesis
Embryonic development
Embryos
Endocrine disruptors
Enzymes
Fish
Gene expression
Gene regulation
Genes
Genetic aspects
Homeostasis
Hormones
Hypoxia
Hypoxia-inducible factor 1
Hypoxia-inducible factors
Laboratories
Original Research
Peer review
Physiological aspects
Proline
Proteins
Sperm
Steroidogenesis
Studies
Transcription
Zebrafish
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Summary:Hypoxia is an important environmental stressor leading to endocrine disruption and reproductive impairment in fish. Although the hypoxia-inducible factor 1 (HIF-1) is known to regulate the transcription of various genes mediating oxygen homeostasis, its role in modulating steroidogenesis-related gene expression remains poorly understood. In this study, the regulatory effect of HIF-1 on the expression of 9 steroidogenic enzyme genes was investigated in zebrafish embryos using a ＂gain-of-function and loss-of-function＂ approach. Eight of the genes, CYP11a, CYP11b2, 3β-HSD, HMGCR, CYP17a1, 17β-HSD2, CYP19a, and CYP19b, were found to be differentially upregulated at 24 and 48 hpf following zHIF-1α-ΔODD overexpression (a mutant zebrafish HIF-1α protein with proline-414 and proline-557 deleted). Knockdown of zHIF-1α also affected the expression pattern of the steroidogenic enzyme genes. Overexpression of zHIF-1α and hypoxia exposure resulted in downregulated StAR expression but upregulated CYP11a and 3β-HSD expression in zebrafish embryos. Conversely, the expression patterns of these 3 genes were reversed in embryos in which zHIF-1α was knocked down under normoxia, suggesting that these 3 genes are regulated by HIF-1. Overall, the findings from this study indicate that HIF-1–mediated mechanisms are likely involved in the regulation of specific steroidogenic genes.
ISSN:1177-6250
1177-6250
DOI:10.1177/1177625017713193