Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

Hanna K.L. Johansson, Pauliina Damdimopoulou, Majorie B.M. van Duursen, Julie Boberg, Delphine Franssen, Marijke de Cock, Kersti Jääger, Magdalena Wagner, Agne Velthut-Meikas, Yuling Xie, Lisa Connolly, Pauline Lelandais, Severine Mazaud-Guittot, Andres Salumets, Monica Kam Draskau, Panagiotis Filis, Paul A. Fowler, Sofie Christiansen, Anne Simone Parent, Terje Svingen*

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause–effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman’s reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause–effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.

Original languageEnglish
Pages (from-to)3359-3379
Number of pages21
JournalArchives of Toxicology
Issue number10
Early online date7 Jul 2020
Publication statusPublished - Oct 2020


  • Adverse outcome pathway
  • AOP
  • EDC
  • Endocrine-disrupting chemicals
  • ODS
  • Ovarian dysgenesis syndrome
  • Ovary
  • Reproduction


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