Endocrine Disruption and Reproductive Pathology

Belcher, Scott M.; Cline, J. Mark; Conley, Justin M.; Groeters, Sibylle; Jefferson, Wendy N.; Law, Mac; Mackey, Emily; Suen, Alisa A.; Williams, C. N.; Dixon, Darlene; Wolf, Jeffrey C.

doi:10.1177/0192623319879903

Cited by 13 publications

(6 citation statements)

References 152 publications

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“…Results of the Core guideline study were published in a single report [ 2 ], and results of several academic studies were published independently in peer-reviewed journals [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] ]. Assessments of the overall study design [ 18 , 19 ] and a summary of available datasets from multiple CLARITY-BPA studies [ 20 ] are also published in peer-reviewed journals.…”

Section: Introductionmentioning

confidence: 99%

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Heindel

Belcher

Flaws

et al. 2020

Reproductive Toxicology

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Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA) was a comprehensive "industry-standard" Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically-and toxicologically-relevant.

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Section: Introductionmentioning

confidence: 99%

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Heindel

Belcher

Flaws

et al. 2020

Reproductive Toxicology

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“…If compared to the performance of two or three separate tests (TG 229, TG 234, and TG 231), the use of the iFEDT not only leads to a significant overall reduction in the number of fish and potentially waiving of amphibian testing (i.e., highly compatible with 3Rs concept by Russell and Burch [1959]) but also keeps experimental costs and efforts low. Moreover, multigeneration studies automatically include the potential to reveal transgenerational effects, which have repeatedly been discussed in conjunction with endocrine disruption (Belcher et al, 2019; Brehm & Flaws, 2019; Hamid et al, 2021; Huang et al, 2022; López‐Rodríguez et al, 2021; Windsor et al, 2018). In fact, the impact of the two model EDCs could be detected in both the F 0 and the F 1 generations, suggesting potential impact of parental exposure on the offspring.…”

Section: Discussionmentioning

confidence: 99%

Development of the integrated fish endocrine disruptor test (iFEDT)—Part A: Merging of existing fish test guidelines

Pannetier,

Gölz,

Pissarreira Mendes Fagundes

et al. 2023

Integr Envir Assess & Manag

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There has been increasing interest in endocrine disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide use and the increasing evidence of detrimental effects on humans and the environment. However, test systems for the detection of potential EDCs as well as testing strategies still require optimization. Thus, the aim of the present project was the development of an integrated test protocol that merges the existing OECD test guidelines (TGs) 229 (FSTRA − Fish Short‐Term Reproduction Assay) and 234 (FSDT − Fish Sexual Development Test) and implements thyroid‐related endpoints for fish. The “integrated Fish Endocrine Disruptor Test” (iFEDT) represents a comprehensive approach for fish testing, which covers reproduction, early development and sexual differentiation and will thus allow the identification of multiple endocrine‐disruptive effects in fish. Using zebrafish (Danio rerio) as a model organism, two exposure tests were performed with well‐studied EDCs: propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis and 17α‐ethinylestradiol (EE2), an estrogen receptor agonist. In part A of this publication, the effects of PTU and EE2 on established endpoints of the two existing TGs are reported, whereas part B (Gölz et al. 2023) focusses on the novel thyroid‐related endpoints. Results of part A document that, as expected, both PTU and EE2 had strong effects on various endocrine‐related endpoints in zebrafish and their offspring. Merging of TGs 229 and 234 proved feasible, and all established biomarkers and endpoints were responsive as expected, including reproductive and morphometric changes (PTU and EE2), vitellogenin levels, sex ratio, gonad maturation and histopathology (only for EE2) of different life‐stages. A validation of the iFEDT with other well‐known EDCs will allow verifying the sensitivity and usability and confirm its capacity to improve the existing testing strategy for EDCs in fish.

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“…Even though many in vitro assay-based screening systems are available for high throughput screening, most purified small chemical components directly derived from herbs still suffer from marginal potency, adverse effects, and low bioavailability in animal or clinical studies (Belcher et al, 2019;Liu et al, 2019a;Teijaro et al, 2019). For example, the compound rhein showed beneficial effects on diabetic nephropathy, which is related to reduced levels of TGF-β 1 , renal fibrosis, metabolism, and oxidative stress status (Hu et al, 2019).…”

Section: Current Advances In Identification Of Active Components Frommentioning

confidence: 99%

Role of gut microbiota in identification of novel TCM-derived active metabolites

Lin

Lai

et al. 2020

Protein Cell

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Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

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Endocrine Disruption and Reproductive Pathology

Cited by 13 publications

References 152 publications

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Development of the integrated fish endocrine disruptor test (iFEDT)—Part A: Merging of existing fish test guidelines

Role of gut microbiota in identification of novel TCM-derived active metabolites

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