PUBLICATION
Effects of azocyclotin on gene transcription and steroid metabolome of hypothalamic-pituitary-gonad axis, and their consequences on reproduction in zebrafish (Danio rerio)
- Authors
- Ma, Y.N., Cao, C.Y., Wang, Q.W., Gui, W.J., Zhu, G.N.
- ID
- ZDB-PUB-160831-9
- Date
- 2016
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 179: 55-64 (Journal)
- Registered Authors
- Keywords
- Azocyclotin, Endocrine disruption, Reproductive toxicity, Steroid metabolome, Zebrafish
- MeSH Terms
-
- Animals
- Aromatase/genetics
- Aromatase/metabolism
- Down-Regulation/drug effects
- Endocrine Disruptors/chemistry
- Endocrine Disruptors/toxicity*
- Female
- Gonads/drug effects
- Gonads/metabolism
- Hypothalamus/drug effects
- Hypothalamus/metabolism
- Liver/drug effects
- Liver/metabolism
- Male
- Metabolome/drug effects*
- Organotin Compounds/chemistry
- Organotin Compounds/toxicity*
- Pituitary Gland/drug effects
- Pituitary Gland/metabolism
- Real-Time Polymerase Chain Reaction
- Reproduction/drug effects*
- Steroids/metabolism
- Testosterone/analogs & derivatives
- Testosterone/blood
- Transcription, Genetic/drug effects*
- Up-Regulation/drug effects
- Water Pollutants, Chemical/chemistry
- Water Pollutants, Chemical/toxicity*
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 27571716 Full text @ Aquat. Toxicol.
Citation
Ma, Y.N., Cao, C.Y., Wang, Q.W., Gui, W.J., Zhu, G.N. (2016) Effects of azocyclotin on gene transcription and steroid metabolome of hypothalamic-pituitary-gonad axis, and their consequences on reproduction in zebrafish (Danio rerio). Aquatic toxicology (Amsterdam, Netherlands). 179:55-64.
Abstract
The widely used organotins have the potential to disrupt the endocrine system, but little is known of underlying mechanisms of azocyclotin toxicity in fish. The objective of the present study was to investigate the impact of azocyclotin on reproduction in zebrafish. Adult zebrafish were exposed to 0.09 and 0.45μg/L azocyclotin for 21days, and effects on steroid hormones and mRNA expression of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. Mass spectrometry methodology was developed to profile steroids within the metabolome of the gonads. They were disrupted as a result of azocyclotin exposure. Alterations in the expression of key genes associated with reproductive endocrine pathways in the pituitary (lhβ), gonad (cyp19a1a, cyp17a1 and 17β-hsd3), and liver (vtg1, vtg2, cyp1a1, comt, ugt1a and gstp1) were correlated with significant reductions in estrogen in both sexes and increased testosterone in females. Azocyclotin-induced down-regulation of cyp19a1a in males suggested a reduction in the rate of estrogen biosynthesis, while up-regulation of hepatic cyp1a1 and comt in both sexes suggested an increase in estrogen biotransformation and clearance. Azocyclotin also induced change in the expression of 17β-hsd3, suggesting increased bioavailability of 11-ketotestosterone (11-KT) in the blood. Furthermore, the down-regulation of lhβ expression in the brains of azocyclotin-exposed fish was associated with inhibition of oocyte maturation in females and retarded spermatogenesis in males. As a histological finding, retarded development of the ovaries was found to be an important cause for decreased fecundity, with down-regulation of vtg suspected to be a likely underlying mechanism. Additionally, relatively high concentrations of azocyclotin in the gonads may have directly caused toxicity, thereby impairing gametogenesis and reproduction. Embryonic or larval abnormalities occurred in the F1 generation along with accumulated burdens of azocyclotin in F1 eggs, following parental exposure. Overall, our results indicate that exposure to azocyclotin can impair reproduction in fish, and induce toxicity related abnormalities in non-exposed offspring.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping