Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals
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REVIEW ARTICLE
Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals Hanna K. L. Johansson1 · Pauliina Damdimopoulou2 · Majorie B. M. van Duursen3 · Julie Boberg1 · Delphine Franssen4 · Marijke de Cock5 · Kersti Jääger6 · Magdalena Wagner2 · Agne Velthut‑Meikas6,7 · Yuling Xie8 · Lisa Connolly8 · Pauline Lelandais9 · Severine Mazaud‑Guittot9 · Andres Salumets6,10,11 · Monica Kam Draskau1 · Panagiotis Filis12 · Paul A. Fowler12 · Sofie Christiansen1 · Anne‑Simone Parent4,13 · Terje Svingen1 Received: 31 March 2020 / Accepted: 30 June 2020 © The Author(s) 2020
Abstract 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. Keywords Ovary · Reproduction · Adverse outcome pathway · AOP · Ovarian dysgenesis syndrome · ODS · Endocrinedisrupting chemicals · EDC
Introduction A woman’s reproductive health affects numerous aspects of her life, from the ability to conceive to personal wellbeing and social standing. It is also of paramount importance for society more broadly, as it has direct consequences for overall birth rates, health of offspring, and national health budgets. Therefore, any factor that can negatively influence female reproductive development or function should be of utmost concern and efforts put in place to minimize potentially harmful effects. In recent years, a growing body of evidence points towards an association between exposure * Terje Svingen [email protected] Extended author information available on
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