Testing of female reproductive disorders
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LETTER TO THE EDITOR, NEWS AND VIEWS
Testing of female reproductive disorders Hermann M. Bolt1 Received: 10 August 2020 / Accepted: 13 August 2020 © The Author(s) 2020
Recently, Johansson and colleagues published an article about the mechanisms causing female reproductive disorders with a special focus on the ovaries (Johansson et al. 2020). Disturbed ovarian development is referred to as the ovarian dysgenesis syndrome (Buck Louis et al. 2011; Johansson et al. 2017) and a discussion is ongoing if and to which degree environmental factors may contribute (Fowler et al. 2012; Hunt et al. 2016; Johansson et al. 2017). In the present study, the authors established several adverse outcome pathways (AOPs) using the AOP standard terminology (Leist et al. 2017; Vinken et al. 2017). According to Johansson et al., the most relevant AOPs are (1) aromatase (Cyp19a1) reduction, (2) disrupted meiosis, (3) ectopic estradiol or AHR activation, (4) disrupted folliculogenesis and (5) disrupted follicle maturation. The practical relevance is that key events of these AOPs can be tested in cell culture, thereby linking an adverse outcome in humans to in vitro testable readouts. In recent years, stem cell-based tests have been established where precursor cells are exposed to test compounds during the differentiation period (Krug et al. 2013; Waldmann et al. 2014; 2017; Zimmer et al. 2014). Based on in vitro gene expression data, it was possible to identify developmental toxicants and to differentiate them from negative control compounds (Balmer et al. 2014; Weng et al. 2014; Shinde et al. 2015; 2016, 2017). However, in vitro systems of the ovary that reliably represent the human situation still remain to be established and validated. A further challenge to be addressed is scaling, i.e., to identify if—and if yes by which factor—higher concentrations have to be used in vitro compared to the plasma peak concentrations in vivo (Albrecht et al., 2019; Godoy et al., 2013). Although the recently published AOPs of Johansson and colleagues (2020) are an important step towards a more systematic * Hermann M. Bolt [email protected] 1
Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139 Dortmund, Germany
analysis of female reproductive disorders, there is still a long way to go until cause–effect relationships between chemical exposure and reproductive disorders can be reliably established. Acknowledgements Open Access funding provided by Projekt DEAL.
Compliance with ethical standards Conflict of interest The author declares no conflict of interest. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons
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