Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders

Sédes, Lauriane; Desdoits-Lethimonier, Christèle; Rouaisnel, Betty; Holota, Hélène; Thirouard, Laura; Lesné, Laurianne; Damon-Soubeyrand, Christelle; Martinot, Emmanuelle; Saru, Jean-Paul; Mazaud-Guittot, Séverine; Caira, Françoise; Beaudoin, Claude; Jégou, Bernard; Volle, David H.

doi:10.1016/j.stemcr.2018.08.018

Cited by 17 publications

(16 citation statements)

References 43 publications

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“…Using an ex vivo model system, stigmasterol co-exposed with BPA significantly decreased Sertoli cell number, showing the additive effect of both molecules on testis function. However, defects of spermatogenesis and lower sperm production were almost unaffected in Fxrα deficient male mice, suggesting an involvement of FXRα in the effects of BPA co-exposure (Sèdes et al 2018). Based on in vitro data in GC1-spg cells, BPA might act in part as a downregulator of Fxrα expression, and stigmasterol as direct antagonist of FXRα in GC1-spg cells, similarly observed in vivo that could explain the synergistic impact of BPA-stigmasterol exposure (Sèdes et al 2018).…”

Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 84%

“…Finally, stigmasterol is a potent antagonist of the critical nuclear receptor bile acid sensor FXR (farnesoid X receptor, NRIH4) that aids regulation of essential liver gene expression (Carter et al 2007). Co-exposure of BPA with stigmasterol decreased accumulation of FXRα mRNA (Sèdes et al 2018). BPA-stigmasterol co-exposed male mice from postcoitum day 6.5 (PC 6.5) up to 5 days after birth showed impaired fertility of adult male mice originated from altered spermatogenesis, resulting in lower number of Sertoli cells.…”

Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 96%

“…Dietary supplements or natural chemicals can also enhance adverse side effects of BPA when co-exposed. Four studies have been published in the literature that demonstrate adverse outcomes when dietary or naturally occurring compounds are co-exposed with BPA (Branco and Lemos 2014;Ribeiro-Varandas et al 2014;Leung et al 2017;Sèdes et al 2018).…”

Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 99%

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Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

Sonavane

Gassman

2019

Critical Reviews in Toxicology

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Bisphenol A (BPA) is an environmental endocrine disrupting chemical widely used in the production of consumer products, such as polycarbonate plastics, epoxies and thermal receipt paper. Human exposure to BPA is ubiquitous due to its high-volume production and use. BPA exposure has been associated with obesity, diabetes, reproductive disorders and cancer. Yet, the molecular mechanisms or modes of action underlying these disease outcomes are poorly understood due to the pleiotropic effects induced by BPA. A further confounding factor in understanding BPA's impact on human health is that co-exposure of BPA with endogenous and exogenous agents occurs during the course of daily life. Studies investigating BPA exposure effects and their relationship to adverse health outcomes often ignore interactions between BPA and other chemicals present in the environment. This review examines BPA co-exposure studies to highlight potentially unexplored mechanisms of action and their possible associations with the adverse health effects attributed to BPA. Importantly, both adverse and beneficial co-exposure effects are observed between BPA and natural chemicals or environmental stressors in in vitro and in vivo models. These interactions clearly influence cellular responses and impact endpoint measures and need to be considered when evaluating BPA exposures and their health effects.

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Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 84%

Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 96%

Section: Co-exposure With Dietary or Naturally Occurring Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

Sonavane

Gassman

2019

Critical Reviews in Toxicology

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“…One would expect that FXRα might also crosstalk with other NRs such as CAR, since impaired spermatogenesis due to the higher germ cell apoptosis observed in Fxrα -/- male mice fed CA-supplemented diet is reversed by co-administration of the CAR agonist TCPOBOP, while the CAR inverse agonist androstanol can reproduce these defects in wild-type mice after two weeks of treatment [ 155 ]. Moreover, the recent demonstration that the FXRα antagonist stigmasterol can modulate the adverse events of the common environmental chemical bisphenol A (BPA) on testis development and spermatogenesis is questionable, since natural ligands of FXRα with antagonist properties might dramatically accelerate germ cell loss by external factors, including environmental toxicants, leading to reduced fertility ( Figure 3 and [ 157 ]).…”

Section: Bile Acid/xenobiotic Nuclear Receptors In Testis: Protectmentioning

confidence: 99%

Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases

Garcia

Thirouard

Sédes

et al. 2018

IJMS

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Structural and functional studies have provided numerous insights over the past years on how members of the nuclear hormone receptor superfamily tightly regulate the expression of drug-metabolizing enzymes and transporters. Besides the role of the farnesoid X receptor (FXR) in the transcriptional control of bile acid transport and metabolism, this review provides an overview on how this metabolic sensor prevents the accumulation of toxic byproducts derived from endogenous metabolites, as well as of exogenous chemicals, in coordination with the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Decrypting this network should provide cues to better understand how these metabolic nuclear receptors participate in physiologic and pathologic processes with potential validation as therapeutic targets in human disabilities and cancers.

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“…In addition, 2 and 20 μg/kgbw of BPA induced oxidative stress in epididymal spermatozoa, caused abnormalities in sperm morphology, and decreased epididymal sperm counts and motility ( 129 ). When mice were administered 50 mg/kg/day of BPA, the seminiferous tubule contained a lower number of germ cells and undifferentiated germ cells ( 130 ). BPS at a dosage of 50 μg/L induced the generation of reactive oxygen species (ROS) and the apoptosis in germ cells ( 131 ).…”

Section: Bisphenols Sertoli Cells and Male Reproductive Healthmentioning

confidence: 99%

Bisphenols Threaten Male Reproductive Health via Testicular Cells

2020

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Male reproductive function and health are largely dependent on the testes, which are strictly regulated by their major cell components, i. e., Sertoli, Leydig, and germ cells. Sertoli cells perform a crucial phagocytic function in addition to supporting the development of germ cells. Leydig cells produce hormones essential for male reproductive function, and germ cell quality is a key parameter for male fertility assessment. However, these cells have been identified as primary targets of endocrine disruptors, including bisphenols. Bisphenols are a category of man-made organic chemicals used to manufacture plastics, epoxy resins, and personal care products such as lipsticks, face makeup, and nail lacquers. Despite long-term uncertainty regarding their safety, bisphenols are still being used worldwide, especially bisphenol A. While considerable attention has been paid to the effects of bisphenols on health, current bisphenol-related reproductive health cases indicate that greater attention should be given to these chemicals. Bisphenols, especially bisphenol A, F, and S, have been reported to elicit various effects on testicular cells, including apoptosis, DNA damage, disruption of intercommunication among cells, mitochondrial damage, disruption of tight junctions, and arrest of proliferation, which threaten male reproductive health. In addition, bisphenols are xenoestrogens, which alter organs and cells functions via agonistic or antagonistic interplay with hormone receptors. In this review, we provide in utero, in vivo, and in vitro evidence that currently available brands of bisphenols impair male reproductive health through their action on testicular cells.

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Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders

Cited by 17 publications

References 43 publications

Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases

Bisphenols Threaten Male Reproductive Health via Testicular Cells

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