PUBLICATION
Dydrogesterone and levonorgestrel at environmentally relevant concentrations have antagonist effects with rhythmic oscillation in brain and eyes of zebrafish
- Authors
- Shi, W.J., Long, X.B., Li, S.Y., Ma, D.D., Liu, F., Zhang, J.G., Lu, Z.J., Ying, G.G.
- ID
- ZDB-PUB-220506-25
- Date
- 2022
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 248: 106177 (Journal)
- Registered Authors
- Keywords
- Antagonist effects, Mixtures exposure, Progestin, Rhythmic oscillation
- MeSH Terms
-
- Animals
- Brain/metabolism
- Dydrogesterone*
- Levonorgestrel/toxicity
- Male
- Period Circadian Proteins/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism
- PubMed
- 35512552 Full text @ Aquat. Toxicol.
Citation
Shi, W.J., Long, X.B., Li, S.Y., Ma, D.D., Liu, F., Zhang, J.G., Lu, Z.J., Ying, G.G. (2022) Dydrogesterone and levonorgestrel at environmentally relevant concentrations have antagonist effects with rhythmic oscillation in brain and eyes of zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 248:106177.
Abstract
Synthetic progestins levonorgestrel (LNG) and dydrogesterone (DDG) are frequency detected in surface water. Combined effects of LNG and DDG on gonad differentiation are similar to LNG single exposure in juvenile zebrafish. However, LNG and DDG mixtures have stronger effects on spermatogenesis in testes of adult zebrafish, which show variable at different life stage. Effects of LNG and DDG mixtures on eyes and brain remain unknown. Here we investigated effects of LNG, DDG and their mixtures on eyes and brain. Zebrafish were exposed to LNG, DDG and their mixtures from 2 hpf to 144 dpf. Rhythm and vision related biological processes were enriched in eyes and brain in LNG and DDG treatments, which indicated rhythmic oscillation in eyes and brain. The qPCR data revealed that both LNG and DDG decreased transcription of arntl2 and clocka, while increased transcription of per1a, per1b, rpe65a and tefa in eyes and brain. However, DDG and LNG mixtures had slight effect on transcription of genes related to rhythm and vision. In addition, LNG and DDG reduced the thickness of inner nuclear layer in the eyes. Bliss independent model revealed that LNG and DDG had antagonist effects on transcription and histology in eyes and brain. Moreover, LNG and DDG formed the same hydrogen bonds with green-sensitive opsin-4 and rhodopsin kinase GRK7a. Taken together, LNG and DDG competed with each other for the same binding residues resulting in antagonist effect in their mixtures treatments, and have significant ecological implications to assess combined effects of progestins mixtures on fish in different organs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping