The Primodos components Noretheristerone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafish embryos

Samantha Brown, Lucas Rosa Fraga, Gary Cameron, Lynda Erskine, Neil Vargesson (Corresponding Author)

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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.
Original languageEnglish
Article number2917
JournalScientific Reports
Publication statusPublished - 13 Feb 2018



  • hormone pregnancy test
  • cell deth
  • cell proliferation
  • HUVEC assay
  • mouse retinal explant cultures
  • drug screening
  • mass spectroscopy

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