PUBLICATION

Progestins and anti-progestins affect gene expression in early development in zebrafish (Danio rerio) at environmental concentrations

Authors
Zucchi, S., Castiglioni, S., and Fent, K.
ID
ZDB-PUB-120409-9
Date
2012
Source
Environmental science & technology   46(9): 5183-5192 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Gene Expression Regulation, Developmental/drug effects*
  • Progestins/antagonists & inhibitors
  • Progestins/pharmacology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
PubMed
22475373 Full text @ Env. Sci. Tech.
CTD
22475373
Abstract

Progesterone (P4) and synthetic progestins (gestagens) from contraceptives and hormone therapy occur in treated wastewater and surface water, and they may have adverse effects on aquatic organisms. Little is known about the molecular and reproductive effects of P4 and synthetic progestins in fish, and effects of the antiprogestin mifepristone (RU486, an abortive) are unknown. We aimed at elucidating effects on the hormone system by quantitative determination of transcriptional changes of target genes induced by 2, 20 and 200 ng/L P4, RU486, norethindrone (NET) and levonorgestrel (LNG). We exposed zebrafish embryos for 144 hours post fertilization (hpf) to these compounds and analyzed expressional changes of ar, esr1, vtg1, hsd17Β3, and progesterone (pgr), mineralo- (mr) and glucocorticoid (gr) receptors, each at 48, 96 and 144 hpf. Concentrations of NET and LNG were constant during exposure, while P4 and RU486 decreased. P4 and RU486 were the most potent steroids. Significant up to 4-fold induction of pgr, ar, mr and hsd17b3 occurred at 2 ng/L P4 and higher, while RU484 inhibited pgr expression. NET and LNG modulated some transcripts mainly above 2 ng/L. The expressional chances occurring at environmental levels may translate to negative interference with differentiation of brain and gonads, and consequently reproduction.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping