Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle

Viguié, Catherine; Mhaouty-Kodja, Sakina; Habert, René; Chevrier, Cécile; Michel, Cécile; Pasquier, Elodie

doi:10.1016/j.mce.2018.02.007

Cited by 29 publications

(11 citation statements)

References 94 publications

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“…There are strong indications to link EDC exposure to POI, however, except for cigarette smoking, there is a lack of relevant human data addressing this [9]. Furthermore, disturbances of hormone levels-e.g., by BPA [10]-can cause menstrual cycle irregularities as well as affect the quantity and quality of available oocytes.…”

Section: Female Reproductive Healthmentioning

confidence: 99%

“…It is clear though, that some EDCs can affect menstrual cyclicity. For example, an in-depth review clearly shows that an alteration of the HPG axis regulation of oestrogens by BPA is an essential mechanism underlying the observed menstrual cycle irregularities observed with BPA exposure [10]. Some studies show that the rate of folliculogenesis and steroidogenesis are reduced in women treated with ketoconazole during fertility treatment [31,32].…”

Section: Adulthoodmentioning

confidence: 99%

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Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project

Duursen

Boberg

Christiansen

et al. 2020

IJMS

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Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally.

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Section: Female Reproductive Healthmentioning

confidence: 99%

Section: Adulthoodmentioning

confidence: 99%

Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project

Duursen

Boberg

Christiansen

et al. 2020

IJMS

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“…In adult rats, bisphenol A exposure can cause a decreased number of antral follicles and corpora lutea , as well as disrupted estrous cycle associated with delayed and lower amplitude LH surge (López-Rodríguez et al 2019 ). Numerous studies link bisphenol A exposure to aromatase inhibition in granulosa cells and delay or suppression of LH surge resulting in modified ovarian cyclicity (Viguié et al 2018 ). Di-(2-ethylhexyl) adipate can shorten the average length of the estrus cycle in rats (Wato et al 2009 ), whereas acetyl tributyl citrate has been shown to do so in mice (Rasmussen et al 2017 ).…”

Section: Adverse Outcome Pathways As They Relate To Key Processes In mentioning

confidence: 99%

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

et al. 2020

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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.

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“…However, exposure to low doses of BPA results in a variety of adverse effects in rodent in vivo and in vitro studies such as altered development of fetal testes tissue, decreased testosterone secretion in adult testis, altered ovarian cyclicity, and altered brain hormone levels and structure from developmental exposure (Richter et al 2007;Eladak et al 2015;Ullah et al 2018;Viguié et al 2018). Although the mechanism of action for BPA that leads to these effects is not entirely defined, it appears that BPA can act potently through nonclassical estrogen pathways (Alonso-Magdalena et al 2012) as well as alter expression of critical steroidogenesis enzymes such as aromatase (Viguié et al 2018). Even though the level of BPA in water is often too low to be captured in an EDA utilizing a bioassay based on binding to ERα and/or ERβ, that level may be biologically relevant to fish.…”

Section: Eac Modes Of Actionmentioning

confidence: 99%

Factors Affecting Sampling Strategies for Design of an Effects‐Directed Analysis for Endocrine‐Active Chemicals

Brennan

Gale

Alvarez

et al. 2020

Enviro Toxic and Chemistry

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Effects‐directed analysis (EDA) is an important tool for identifying unknown bioactive components in a complex mixture. Such an analysis of endocrine‐active chemicals (EACs) from water sources has promising regulatory implications but also unique logistical challenges. We propose a conceptual EDA (framework) based on a critical review of EDA literature and concentrations of common EACs in waste and surface waters. Required water volumes for identification of EACs under this EDA framework were estimated based on bioassay performance (in vitro and in vivo bioassays), limits of quantification by mass spectrometry (MS), and EAC water concentrations. Sample volumes for EDA across the EACs showed high variation in the bioassay detectors, with genistein, bisphenol A, and androstenedione requiring very high sample volumes and ethinylestradiol and 17β‐trenbolone requiring low sample volumes. Sample volume based on the MS detector was far less variable across the EACs. The EDA framework equation was rearranged to calculate detector “thresholds,” and these thresholds were compared with the literature EAC water concentrations to evaluate the feasibility of the EDA framework. In the majority of instances, feasibility of the EDA was limited by the bioassay, not MS detection. Mixed model analysis showed that the volumes required for a successful EDA were affected by the potentially responsible EAC, detection methods, and the water source type, with detection method having the greatest effect on the EDA of estrogens and androgens. The EDA framework, equation, and model we present provide a valuable tool for designing a successful EDA. Environ Toxicol Chem 2020;39:1309–1324. © 2020 SETAC

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Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle

Cited by 29 publications

References 94 publications

Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project

Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project

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

Factors Affecting Sampling Strategies for Design of an Effects‐Directed Analysis for Endocrine‐Active Chemicals

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