Endocrine disrupting potential of replacement flame retardants – Review of current knowledge for nuclear receptors associated with reproductive outcomes

Bajard, Lola; Negi, Chander K.; Mustieles, Vicente; Melymuk, Lisa; Jomini, Stéphane; Barthelemy-Berneron, Johanna; Fernández, Mariana F.; Bláha, Luděk

doi:10.1016/j.envint.2021.106550

Cited by 31 publications

(10 citation statements)

References 96 publications

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“…Measurable levels of PBDEs are also detected in women's follicular fluid, suggesting that flame retardants can target the ovary. This is concerning because both PBDEs and PFRs have estrogenic activities, interact with pregnane X receptors, estrogen receptors, and P 4 receptors, and can interfere with steroid hormone homeostasis (Bajard et al, 2021 ; Czerska et al, 2013 ; Meerts et al, 2001 ). Their impacts on ovarian and ovulatory endpoints are summarized in Figure 2 .…”

Section: Flame Retardantsmentioning

confidence: 99%

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

Land

Miller

Fugate

et al. 2022

Molecular Reproduction Devel

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Exposure to endocrine‐disrupting chemicals (EDCs) is unavoidable, which represents a public health concern given the ability of EDCs to target the ovary. However, there is a large gap in the knowledge about the impact of EDCs on ovarian function, including the process of ovulation. Defects in ovulation are the leading cause of infertility in women, and EDC exposures are contributing to the prevalence of infertility. Thus, investigating the effects of EDCs on the ovary and ovulation is an emerging area for research and is the focus of this review. The effects of EDCs on gametogenesis, uterine function, embryonic development, and other aspects of fertility are not addressed to focus on ovarian‐ and ovulation‐related fertility issues. Herein, findings from epidemiological and basic science studies are summarized for several EDCs, including phthalates, bisphenols, per‐ and poly‐fluoroalkyl substances, flame retardants, parabens, and triclosan. Epidemiological literature suggests that exposure is associated with impaired fecundity and in vitro fertilization outcomes (decreased egg yield, pregnancies, and births), while basic science literature reports altered ovarian follicle and corpora lutea numbers, altered hormone levels, and impaired ovulatory processes. Future directions include identification of the mechanisms by which EDCs disrupt ovulation leading to infertility, especially in women.

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Section: Flame Retardantsmentioning

confidence: 99%

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

Land

Miller

Fugate

et al. 2022

Molecular Reproduction Devel

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“…Several health hazards associated with exposure to EHDPP, such as endocrine disruption developmental and neurotoxicity in in vitro cell culture and experimental animal models, have already been reported. − In addition, recent evidence highlights the metabolic disrupting potential of EHDPP in mice, where prenatal exposure affected the metabolic phenotype of male offspring . Comparable effects were also noted in a few other in vitro studies, for instance, EHDPP-mediated induction of adipogenesis in mouse 3T3-L1 preadipocytes through the peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway, hepatotoxic effects in human fetal hepatocyte (L02) cells at the level of transcriptome, etc.…”

Section: Introductionmentioning

confidence: 97%

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Negi

Gadara

Kohoutek

et al. 2023

Environ. Sci. Technol.

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The present study aims to evaluate the effects of repeated exposure to 2-ethylhexyldiphenyl phosphate (EHDPP) on human liver cells. In vitro three-dimensional (3D) hepatospheroid cell culture was utilized to explore the potential mechanisms of EHDPP-mediated metabolic disruption through morphological, transcriptional, and biochemical assays. Lipidomics analysis was performed on the individual hepatospheroids to investigate the effects on intracellular lipid profiles, followed by hepatospheroid morphology, growth, functional parameters, and cytotoxicity evaluation. The possible mechanisms were delineated using the gene-level analysis by assessing the expression of key genes encoding for hepatic lipid metabolism. We revealed that exposure to EHDPP at 1 and 10 μM for 7 days alters the lipid profile of human 3D hepatospheroids. Dysregulation in several lipid classes, including sterol lipids (cholesterol esters), sphingolipids (dihydroceramide, hexosylceramide, ceramide, sphingomyelin), glycerolipids (triglycerides), glycerophospholipids, and fatty acyls, was noted along with alteration in genes including ACAT1, ACAT2, CYP27A1, ABCA1, GPAT2, PNPLA2, PGC1α, and Nrf2. Our study brings a novel insight into the metabolic disrupting effects of EHDPP and demonstrates the utility of hepatospheroids as an in vitro cell culture model complemented with omics technology (e.g., lipidomics) for mechanistic toxicity studies.

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“…Flame retardants were identified by European Union (EU) institutions and HBM4EU partner countries as priority substances to be studied as knowledge gaps with an impact on regulation still exist ( Louro et al, 2019 ). Several detrimental ecological and human health issues have been associated with elevated FR concentrations, including environmental persistence, long-range transport, bioaccumulation, and endocrine and neurologically disruptive effects on organisms, including humans ( Aznar-Alemany et al, 2019 ; Bajard et al, 2019 , 2021 ; Stieger et al, 2014 ; Sverko et al, 2011 )…”

Section: Introductionmentioning

confidence: 99%

Exposure to flame retardants in European children — Results from the HBM4EU aligned studies

Schyff

Kalina

Govarts

et al. 2023

International Journal of Hygiene and Environmental Health

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Endocrine disrupting potential of replacement flame retardants – Review of current knowledge for nuclear receptors associated with reproductive outcomes

Cited by 31 publications

References 96 publications

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

The effects of endocrine‐disrupting chemicals on ovarian‐ and ovulation‐related fertility outcomes

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Exposure to flame retardants in European children — Results from the HBM4EU aligned studies

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