Nonsteroidal anti-inflammatory drugs (NSAIDs) cause male-biased sex differentiation in zebrafish

Autor: Per-Erik Olsson, Ajay Pradhan, Ceyhun Bereketoglu
Přispěvatelé: Mühendislik ve Doğa Bilimleri Fakültesi -- Biyomedikal Mühendisliği Bölümü, Bereketoğlu, Ceyhun
Rok vydání: 2019
Předmět:
Ketoprofen
Male
Embryo
Nonmammalian
Ibuprofen
Apoptosis
Pharmacology
Toxicology
Real time polymerase chain reaction
Embryo development
01 natural sciences
Naproxen
WNT4
Follicle rupture
Medicine
skin and connective tissue diseases
Water pollutant
Gene expression regulation
0303 health sciences
Reproduction
Aquatic environment
Long term exposure
Water pollution
Sex ratio
Protein p21
Embryonic Development
digestive system
Concentration (parameter)
03 medical and health sciences
Nonmammalian embryo
Upregulation
Ovulatory process
PPCP | Micropollutant | Carbamazepine
Genetics
Humans
Animal experiment
Adverse effect
Indometacin
Sexual differentiation
Zebra fish
Animal
Sex determination
digestive system diseases
Toxicity testing
Embryonic stages
Gene expression
Sex Differentiation
Health
Toxicology and Mutagenesis
010501 environmental sciences
Inflammatory responses
Marine & Freshwater Biology
Gene-expression
Zebrafish
Nimesulide
Priority journal
Caspase 8
biology
Genetic analysis
Anti-Inflammatory Agents
Non-Steroidal
Gene Expression Regulation
Developmental
Cyprinid
Embryo
Toxicity
Pharmaceuticals
Female
medicine.symptom
Drug
medicine.drug
medicine.drug_class
Danio-rerio
Inflammation
Down regulation
Aquatic Science
Anti-inflammatory
Pain killers
Hatching
Acetylsalicylic acid
Sewage-treatment plants
P21 gene
Animals
Mortality
030304 developmental biology
0105 earth and related environmental sciences
Acute toxicity
business.industry
Casp8 gene
Larval stage
biology.organism_classification
Nonhuman
Metabolism
Celecoxib
Cyclooxygenase 2
Cyclooxygenase 1
business
Controlled study
Water Pollutants
Chemical
Zdroj: Aquatic toxicology (Amsterdam, Netherlands). 223
ISSN: 1879-1514
Popis: WOS: 000531077200005
PubMed ID: 32315829
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used pharmaceuticals to treat pain, fever and inflammation. NSAIDs are also known to have many side effects including adverse effects on reproduction in both humans and animals. As NSAIDs usage is not regulated they are frequently detected at high concentrations in the environment. In order to understand the effect of NSAIDs on zebrafish sex differentiation, we used seven different NSAIDs which were either Cox-1 selective, Cox-1 biased, non-selective or COX-2 selective. We show that at higher concentration, NSAIDs are toxic to zebrafish embryo as they lead to mortality and hatching delay. Gene expression analysis following short term exposure of NSAIDs led to downregulation of female specific genes including zp2, vtg2 foxl2 and wnt4. Long term exposure of larvae to environmentally relevant concentrations of Cox-2 selective and non-selective NSAIDs resulted in male-biased sex ratio which confirmed the qRT-PCR analysis. However, the Cox-1 selective acetylsalicylic acid and the Cox-1 biased ketoprofen did not alter sex ratio. The observed male-biased sex ratio could also be due to induction of apoptosis process as the genes including p21 and casp8 were significantly upregulated following exposure to the Cox-2 selective and the nonselective NSAIDs. The present study indicates that NSAIDs alter sex differentiation in zebrafish, primarily through inhibition of Cox-2. This study clearly demonstrates that the use of NSAIDs and their release into the aquatic environment should be carefully monitored to avoid adverse effects to the aquatic organisms.
Swedish Research CouncilSwedish Research Council [201504600]; Knowledge Foundation Sweden [20150084]; Orebro University
This study was financed by the Swedish Research Council (201504600), the Knowledge Foundation Sweden (20150084), and Orebro University.
Databáze: OpenAIRE
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