- Title
- Leptin-mediated modulation of steroidogenic gene expression in hypoxic zebrafish embryos: implications for the disruption of sex steroids
- Creator
- Yu, Richard Man Kit; Chu, Daniel Ling Ho; Tan, Tian-feng; Li, Vincent Wai Tsun; Chan, Alice Ka Yee; Giesy, John P.; Cheng, Shuk Han; Wu, Rudolf Shiu Sun; Kong, Richard Yuen Chong
- Relation
- Environmental Science & Technology Vol. 46, Issue 16, p. 9112-9119
- Publisher Link
- http://dx.doi.org/10.1021/es301758c
- Publisher
- American Chemical Society
- Resource Type
- journal article
- Date
- 2012
- Description
- Hypoxia can impair reproduction of fishes through the disruption of sex steroids. Here, using zebrafish (Danio rerio) embryos, we investigated (i) whether hypoxia can directly affect steroidogenesis independent of pituitary regulation via modulation of steroidogenic gene expression, and (ii) the role of leptin in hypoxia-induced disruption of steroidogenesis. Exposure of fertilized zebrafish embryos to hypoxia (1.0 mg O₂ L–1) from 0–72 h postfertilization (hpf), a developmental window when steroidogenesis is unregulated by pituitary influence, resulted in the up-regulation of cyp11a, cyp17, and 3β-hsd and the down-regulation of cyp19a. Similar gene expression patterns were observed for embryos exposed to 10 mM cobalt chloride (CoCl₂, a chemical inducer of hypoxia-inducible factor 1, HIF-1), suggesting a regulatory role of HIF-1 in steroidogenesis. Testosterone (T) and estradiol (E2) concentrations in hypoxic embryos were greater and lesser, respectively, relative to the normoxic control, thus leading to an increased T/E2 ratio. Expression of the leptin-a gene (zlep-a) was up-regulated upon both hypoxia and CoCl₂ treatments. Functional assays suggested that under hypoxia, elevated zlep-a expression might activate cyp11a and 3β-hsd and inhibit cyp19a. Overall, this study indicates that hypoxia, possibly via HIF-1-induced leptin expression, modulates sex steroid synthesis by acting directly on steroidogenic gene expression.
- Subject
- hypoxia; fish reproduction; zebrafish; <i>Danio rerio</i>; leptin
- Identifier
- http://hdl.handle.net/1959.13/1309076
- Identifier
- uon:21764
- Identifier
- ISSN:0013-936X
- Rights
- This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see see http://pubs.acs.org/page/policy/articlesonrequest/index.html.
- Language
- eng
- Reviewed
- Hits: 6425
- Visitors: 6389
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|