PUBLICATION
The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos
- Authors
- Brown, S., Fraga, L.R., Cameron, G., Erskine, L., Vargesson, N.
- ID
- ZDB-PUB-180223-4
- Date
- 2018
- Source
- Scientific Reports 8: 2917 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Cell Proliferation/drug effects
- Dose-Response Relationship, Drug
- Drug Interactions
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/innervation
- Embryonic Development/drug effects
- Ethinyl Estradiol/analysis
- Ethinyl Estradiol/toxicity*
- Hormones/chemistry*
- Humans
- Mice
- Nervous System/drug effects
- Nervous System/growth & development
- Norethindrone Acetate/analysis
- Norethindrone Acetate/toxicity*
- Pregnancy Tests/adverse effects*
- Time Factors
- Toxicity Tests*
- Zebrafish/embryology*
- PubMed
- 29440757 Full text @ Sci. Rep.
Citation
Brown, S., Fraga, L.R., Cameron, G., Erskine, L., Vargesson, N. (2018) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos. Scientific Reports. 8:2917.
Abstract
Primodos was a hormone pregnancy test used between 1958-1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer used, it's components, Norethisterone acetate and Ethinyl estradiol, are used in other medications today including treatments for endometriosis and contraceptives. However, whether Primodos caused birth defects or not remains controversial, and has been little investigated. Here we used the developing zebrafish embryo, a human cell-line and mouse retinal explants to investigate the actions of the components of Primodos upon embryonic and tissue development. We show that Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems. Moreover, we found that the Norethisterone acetate and Ethinyl estradiol mixture can affect nerve outgrowth and blood vessel patterning directly and accumulates in the forming embryo for at least 24 hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development in the zebrafish. Further work in mammalian model species are now required to build on these findings and determine if placental embryos also are affected by synthetic sex hormones and their mechanisms of action.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping