Next Generation Reproductive and Developmental Toxicology: Crosstalk Into the Future

Hougaard, Karin Sørig

doi:10.3389/ftox.2021.652571

Cited by 14 publications

(14 citation statements)

References 46 publications

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“…Placental toxicity is another key cell type specific aspect of DART ( Gingrich et al, 2020 ). However, the ex vivo or other advanced models of human placenta are still in their early stages of development ( Hougaard, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, we are yet to have a unified database as a resource that can share the available information on epidemiological and environmental aspects or clinical biomarkers for the large number of industrial chemicals and pharmaceutical compounds ( Hougaard, 2021 ). Such a database would be immensely valuable in validating and benchmarking NAMs outputs with the gold standard human evidence.…”

Section: Discussionmentioning

confidence: 99%

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Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

et al. 2022

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New Approach Methodologies (NAMs) promise to offer a unique opportunity to enable human-relevant safety decisions to be made without the need for animal testing in the context of exposure-driven Next Generation Risk Assessment (NGRA). Protecting human health against the potential effects a chemical may have on embryo-foetal development and/or aspects of reproductive biology using NGRA is particularly challenging. These are not single endpoint or health effects and risk assessments have traditionally relied on data from Developmental and Reproductive Toxicity (DART) tests in animals. There are numerous Adverse Outcome Pathways (AOPs) that can lead to DART, which means defining and developing strict testing strategies for every AOP, to predict apical outcomes, is neither a tenable goal nor a necessity to ensure NAM-based safety assessments are fit-for-purpose. Instead, a pragmatic approach is needed that uses the available knowledge and data to ensure NAM-based exposure-led safety assessments are sufficiently protective. To this end, the mechanistic and biological coverage of existing NAMs for DART were assessed and gaps to be addressed were identified, allowing the development of an approach that relies on generating data relevant to the overall mechanisms involved in human reproduction and embryo-foetal development. Using the knowledge of cellular processes and signalling pathways underlying the key stages in reproduction and development, we have developed a broad outline of endpoints informative of DART. When the existing NAMs were compared against this outline to determine whether they provide comprehensive coverage when integrated in a framework, we found them to generally cover the reproductive and developmental processes underlying the traditionally evaluated apical endpoint studies. The application of this safety assessment framework is illustrated using an exposure-led case study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

et al. 2022

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“…Developmental toxicity is defined as any reversible or irreversible functional or structural alteration caused by environmental insult, diet, and toxic chemicals or physical factors that affect organisms’ normal growth, differentiation, development, or behaviour ( Hougaard, 2021 ). In this section, we have discussed the development and growth effects such as fetal growth, deformities, and death in offspring whose parents are exposed to MPs for an extended period.…”

Section: Reproductive Toxic Effects Of Mps Exposurementioning

confidence: 99%

Developmental and reproductive toxic effects of exposure to microplastics: A review of associated signaling pathways

2022

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Microplastics (MPs), small pieces of plastic (∼5 mm), are released into the environment not only as a result of the decomposition of large-sized plastics but also from day-to-day use of plastic products. Chronic exposure to MPs has been attributed to harmful effects on aquatic organisms and rodents. Effects include gastrointestinal toxicity, hepatotoxicity, neurotoxicity, and reproductive and developmental toxicities. Exposure to MPs may also potentially affect human health. Herein, we reviewed the impact of MPs on male and female reproductive systems and the associated mechanisms involved in the reproductive and developmental toxicities of MPs. We performed a literature search in Google Scholar and PubMed using the following keywords: MPs and reproductive toxicity; MPs and developmental studies; MPs and infertility; MPs and aquatics; and MPs and rodents. Evidence of MPs accumulation has been reported in many organs of humans and experimental models. The harmful effects of MPs have been manifested in male and female reproductive systems of mammalian and aquatic animals, including developmental effects on gametes, embryos, and their offspring. This review describes various signaling pathways involved in MPs-associated male and female reproductive and developmental toxicities.

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“…Many stages of perinatal life are vulnerable to disturbances such as exposure to environmental chemicals and drugs that can interfere with molecular and cellular processes. Of concern is the enormous number of chemicals and pharmaceuticals in existence and for which humans and wildlife can be exposed through their life cycles (Rockström et al, 2009;Svingen and Vinggaard, 2016;Hougaard, 2021).Although there are international regulations and guidelines in place for testing and assessing chemical substances for their potential toxicity, they are in many ways inadequate in dealing with the vast number of chemicals in use coupled with the myriad of potential effect they can have on complex living organisms. This challenge is becoming even more pressing with modern toxicology moving towards higher dependence on alternative test methods rather than more traditional large-scale animal toxicity testing for screening and prioritizing chemical substances of concern (Pistollato et al, 2021).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Editorial: Methods and Protocols in Developmental and Reproductive Toxicology

Hougaard

Svingen²

2022

Front. Toxicol.

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Editorial on the Research Topic Methods and Protocols in Developmental and Reproductive ToxicologyUndisturbed reproductive development is a prerequisite for life-long reproductive health. Many stages of perinatal life are vulnerable to disturbances such as exposure to environmental chemicals and drugs that can interfere with molecular and cellular processes. Of concern is the enormous number of chemicals and pharmaceuticals in existence and for which humans and wildlife can be exposed through their life cycles (Rockström et al., 2009;Svingen and Vinggaard, 2016;Hougaard, 2021).Although there are international regulations and guidelines in place for testing and assessing chemical substances for their potential toxicity, they are in many ways inadequate in dealing with the vast number of chemicals in use coupled with the myriad of potential effect they can have on complex living organisms. This challenge is becoming even more pressing with modern toxicology moving towards higher dependence on alternative test methods rather than more traditional large-scale animal toxicity testing for screening and prioritizing chemical substances of concern (Pistollato et al., 2021). This is not least important in hypothesisdriven testing, or predictive toxicology, where knowledge about toxicological mechanisms and measurable key events increasingly feed into causal adverse outcome pathways (AOPs)

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Next Generation Reproductive and Developmental Toxicology: Crosstalk Into the Future

Cited by 14 publications

References 46 publications

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

Developmental and reproductive toxic effects of exposure to microplastics: A review of associated signaling pathways

Editorial: Methods and Protocols in Developmental and Reproductive Toxicology

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