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 24hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development. 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.
The authors thank Amanda Berg, Zoe Finlayson, Lisa Salhi and Elizabeth Stewart, for help with preliminary studies; Alexandra J. Rafipay (nee Diamond) and Jonathan Smith for lab assistance and discussions and Jesse Olszynko-Gryn, Tobias Arndt, Marie Lyon for discussions on Primodos. Lucas Rosa Fraga was funded by a PhD scholarship from the Science without Borders program – CNPq Brazil – INAGEMP/ Grant CNPq 573993/2008-4 and Samantha Brown was funded by a PhD scholarship from the University of Aberdeen.
- hormone pregnancy test
- cell deth
- cell proliferation
- HUVEC assay
- mouse retinal explant cultures
- drug screening
- mass spectroscopy
FingerprintDive into the research topics of 'The Primodos components Noretheristerone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos'. Together they form a unique fingerprint.
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Chair in Developmental Biology
- School of Medicine, Medical Sciences & Nutrition, MRC/Versus Arthritis Centre for Musculoskeletal Health and Work
- Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH)