Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse Spleen

Gear, Robin; Belcher, Scott M.

doi:10.1101/109009

Cited by 7 publications

(10 citation statements)

References 57 publications

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“…Following up on those in vitro findings, in vivo studies using a continuous life‐long dietary exposure protocol of BPA or control 17α‐ethinyloestradiol exposures were performed in CD‐1 mice . BPA exposure spanned five orders of magnitude from ~4 μg/kg BW/d to ~50 000 μg/kg BW/d with a 10‐fold dose interval.…”

Section: Cardiac End‐pointsmentioning

confidence: 99%

“…Three doses of 17α‐ethinyloestradiol resulting in exposures of ~0.02, 0.2 and 0.15 μg/kg BW/d were also included. These studies demonstrated significant, and most often, sex‐specific effects of BPA on a variety of reproductive, metabolic, immune and cardiovascular‐related end‐points . In the heart, only minor exposure‐related increases in heart weight, left ventricular (LV) wall thickness and modest changes in collagen content in the extracellular matrix of hearts were found in males exposed to 430 and 4400 μg BPA/kg BW/d.…”

Section: Cardiac End‐pointsmentioning

confidence: 99%

“…64 Following up on those in vitro findings, in vivo studies using a continuous life-long dietary exposure protocol of BPA or control 17α-ethinyloestradiol exposures were performed in CD-1 mice. 63,[68][69][70][71] BPA exposure spanned five orders of magnitude from~4 μg/kg BW/d to~50 000 μg/kg BW/d with a 10-fold dose interval. Three doses of 17α-ethinyloestradiol resulting in exposures of~0.02, 0.2 and 0.15 μg/kg BW/d were also included.…”

Section: Cardiac End-pointsmentioning

confidence: 99%

“…These studies demonstrated significant, and most often, sex-specific effects of BPA on a variety of reproductive, metabolic, immune and cardiovascular-related end-points. 63,[68][69][70][71] In the heart, only minor exposure-related increases in heart weight, left ventricular (LV) wall thickness and modest changes in collagen content in the extracellular matrix of hearts were found in males exposed to 430 and 4400 μg BPA/kg BW/d. In contrast, modest decreases in LV wall thickness and a remarkable decrease in collagen were observed in hearts of females at the lowest BPA dose (5 μg/kg BW/d).…”

Section: Cardiac End-pointsmentioning

confidence: 99%

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CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

Prins

Patisaul

Belcher

et al. 2018

Basic Clin Pharma Tox

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Bisphenol A (BPA) is a high-production chemical used in a variety of applications worldwide. While BPA has been documented as an endocrine-disrupting chemical (EDC) having adverse health-related outcomes in multiple studies, risk assessment for BPA has lagged due to reliance on guideline toxicology studies over academic ones with end-points considered more sensitive and appropriate. To address current controversies on BPA safety, the United States National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and the Food and Drug Administration (FDA) established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) using the NCTR Sprague-Dawley rats. The goal of CLARITY-BPA is to perform a traditional regulatory toxicology study (Core study) in conjunction with multiple behavioural, molecular and cellular studies by academic laboratories focused on previously identified BPA-sensitive organ systems (Academic studies). Combined analysis of the data from both study types will be undertaken by the NTP with the aim of resolving uncertainties on BPA toxicity. To date, the Core study has been completed and a draft report released. Most of the academic studies have also been finalized and published in peer-reviewed journals. In light of this important milestone, the PPTOX-VI meeting held in the Faroe Islands, 27-30 May 2018 devoted a plenary session to CLARITY-BPA with presentations by multiple investigators with the purpose of highlighting key outcome. This MiniReview synthesizes the results of three academic studies presented at this plenary session, evaluates recently published findings by other CLARITY-BPA academic studies to provide an early combined overview of this emerging data and places this in the context of the Core study findings. This co-ordinated effort revealed a plethora of significant BPA effects across multiple organ systems and BPA doses with non-monotonic responses across the dose range utilized. Remarkably consistent across most studies, including the Core study, are low-dose effects (2.5, 25 and 250 μg BPA/kg body-weight). Collectively, the findings highlighted herein corroborate a significant body of evidence that documents adverse effects of BPA at doses relevant to human exposures and emphasizes the need for updated risk assessment analysis.

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Section: Cardiac End‐pointsmentioning

confidence: 99%

Section: Cardiac End‐pointsmentioning

confidence: 99%

Section: Cardiac End-pointsmentioning

confidence: 99%

Section: Cardiac End-pointsmentioning

confidence: 99%

See 2 more Smart Citations

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

Prins

Patisaul

Belcher

et al. 2018

Basic Clin Pharma Tox

Self Cite

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“…The dosage of EE2 from 0.02 to 200 μg/kg was selected for examining its biological activity in the animal study. However, significant effects of EE2 treatment have been observed among concentrations from 2 to 50 μg/kg 16,19,21,54 . Therefore, in this study, EE2 (Sigma-Aldrich, St Louis, MO, USA) was dissolved in sesame oil (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

Lin

Kuo²,

Chen

et al. 2020

Sci Rep

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The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.The endocrine system precisely mediates sexual development and reproductive ability through circulating sexual hormones, which act as signaling molecules to render adequate regulation. Endocrine-disrupting chemicals (EDCs) are natural or industrial chemicals that are released into the environment through industries, livestock activities, domestic wastewater, and hospital effluence 1,2 . Numerous studies have indicated that EDCs interfere with endogenous endocrine processes by mimicking hormonal action, leading to infertility, metabolic syndrome, and the rise of cancer incidence 3-5 . In humans, increasing studies have indicated that EDCs have detrimental effects on the reproductive system, resulting in poor sperm quality and testicular dysgenic occurrence in men 6,7 , and disorders of ovulation and the uterus as well as a rise in breast cancer incidences in women 8,9 . Hence, the risks of EDCs are a global health issue 10 .EE2 has been reported to exert a higher estrogenic activity than estradiol (E2), and is extremely stable against oxidation by metabolism or degradation in the human body due to the property of the ethynyl group in the C 17 position [11][12][13] . This characteristic potentially allows 17α-ethynylestradiol (EE2) to pass into the environment 14,15 . Therefore, it is reasonable to consider environmental EE2 to be an EDC and have deleterious effects on the health of both animals and human beings 15 . The pharmaceutical EE2 is a synthetic estrogen widely used as an oral contraceptive pill, but abundant animal studies have also reported that long-term exposure to EE2 interferes with the biological ...

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Luteolin promotes KAT6A gene expression

2023

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De novo, rare, and genomic variants in the KAT6A gene have been associated with cases of intellectual disability with speech/language impairment. The pathogenic variants of KAT6A gene can produce the KAT6A enzyme inefficiently, faulty, or in inappropriate quantity. In order to search for compounds able to modulate the KAT6A gene expression, we treated primary human osteoblasts with molecules structurally similar to bisphenol A, a potentially toxic compound known as an upregulator of KAT6A gene expression. We further demonstrated that much safer compounds, such as luteolin and 17 α hydroxyprogesterone, could induce the upregulation of KAT6A gene in human osteoblasts.

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Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse Spleen

Cited by 7 publications

References 57 publications

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol

Luteolin promotes KAT6A gene expression

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