Persistent endocrine-disrupting chemicals found in human follicular fluid stimulate the proliferation of granulosa tumor spheroids via GPR30 and IGF1R but not via the classic estrogen receptors

Gogola-Mruk, Justyna; Hoffmann, Marta; Ptak, Anna

doi:10.1016/j.chemosphere.2018.11.018

Cited by 38 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The evidence for PFAS affecting ER signaling in humans and animals is mixed. Although studies have identified some PFAS as being without estrogenic activity (Behr et al 2018; Borghoff et al 2018; Gogola et al 2019), others suggest an ability of PFAS to modulate or even activate ER‐mediated effects (Benninghoff et al 2010; Kjeldsen and Bonefeld‐Jørgensen 2013; Wang et al 2018; Bjerregaard‐Olesen et al 2019; Qiu et al 2020), with some effects only observed in aquatic organisms (Wei et al 2009; Chen et al 2016, 2018). Microarray analyses of human primary hepatocytes confirmed that PFOA activated the ER pathway (Buhrke et al 2015).…”

Section: Current Knowledge Of Pfas Toxicity In Experimental Modelsmentioning

confidence: 99%

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Fenton

Ducatman

Boobis

et al. 2020

Enviro Toxic and Chemistry

1,120

533

View full text Add to dashboard Cite

Reports of environmental and human health impacts of per‐ and polyfluoroalkyl substances (PFAS) have greatly increased in the peer‐reviewed literature. The goals of the present review are to assess the state of the science regarding toxicological effects of PFAS and to develop strategies for advancing knowledge on the health effects of this large family of chemicals. Currently, much of the toxicity data available for PFAS are for a handful of chemicals, primarily legacy PFAS such as perfluorooctanoic acid and perfluorooctane sulfonate. Epidemiological studies have revealed associations between exposure to specific PFAS and a variety of health effects, including altered immune and thyroid function, liver disease, lipid and insulin dysregulation, kidney disease, adverse reproductive and developmental outcomes, and cancer. Concordance with experimental animal data exists for many of these effects. However, information on modes of action and adverse outcome pathways must be expanded, and profound differences in PFAS toxicokinetic properties must be considered in understanding differences in responses between the sexes and among species and life stages. With many health effects noted for a relatively few example compounds and hundreds of other PFAS in commerce lacking toxicity data, more contemporary and high‐throughput approaches such as read‐across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on emerging and legacy PFAS, individually and as mixtures. In addition, an appropriate degree of precaution, given what is already known from the PFAS examples noted, may be needed to protect human health. Environ Toxicol Chem 2021;40:606–630. © 2020 SETAC

show abstract

Section: Current Knowledge Of Pfas Toxicity In Experimental Modelsmentioning

confidence: 99%

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Fenton

Ducatman

Boobis

et al. 2020

Enviro Toxic and Chemistry

1,120

533

View full text Add to dashboard Cite

show abstract

“…In vitro, PFOA induced cell migration and invasion in human endometrial [205] and ovarian cancer cells [206], mediated by the ERK (extracellular signal-regulated kinase)/mTOR (mammalian target of rapamycin) and the ERK 1/2 nuclear factor-kappaB signaling pathways respectively. In the granulosa tumor spheroid culture model of ovarian cancer, PFOA and PFOS both increased cell proliferation mediated by insulin-like growth-factor 1 receptor [207]. In a human liver cell line, PFOA and PFOS increased the expression of cyclins and cyclin-dependent kinases and induced cell proliferation through G1 to S phase transitions [208,209].…”

Section: Alters Cell Proliferation Cell Death or Nutrient Supplymentioning

confidence: 96%

“…PFOA Association: [61] Association: [202]; [204]; [205]; [207]; [209] Long-chain PFAS a PFOS Association: [203]; [207]; [208]…”

Section: Epidemiological Animal Biosassay In Vitromentioning

confidence: 99%

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

View full text Add to dashboard Cite

Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

show abstract

“…The expression of the Cyp19a1 (Mm00484049_m1) and Hsd3b1 (Mm01261921_mH) genes after 24 h of treatment with the POP mixtures (0.1×, 1×, and 10× dilutions) was measured by real-time PCR, as described previously (Gogola et al 2019). The expression of each was normalised to that of 18S (4310893E), and their relative expression was calculated using the 2 −ΔΔCt method (Livak and Schmittgen 2001).…”

Section: Rt-qpcrmentioning

confidence: 99%

Persistent organic pollutants affect steroidogenic and apoptotic activities in granulosa cells and reactive oxygen species concentrations in oocytes in the mouse

Krawczyk

Marynowicz

Pich

et al. 2022

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

The destruction of granulosa cells (GCs), the main functional cell type in the ovary, prevents steroid hormone production, which in turn may damage oocytes, resulting in ovarian failure. The accumulation of a number of persistent organic pollutants (POPs) in the ovarian follicular fluid (FF) has been documented, which raises serious questions regarding their impact on female fertility. Aims. We aimed to determine whether a mixture of POPs reflecting the profile found in FF influences mouse GCs or oocyte function and viability. Methods. A mixture of POPs, comprising perfluorooctanoate, perfluorooctane sulfonate, 2,2-dichlorodiphenyldichloroethylene, polychlorinated biphenyl 153, and hexachlorobenzene, was used. In addition to using the exact concentration of POPs previously measured in human FF, we tested two other mixtures, one with10-fold lower and another with 10-fold higher concentrations of each POP. Key results. Steroidogenesis was disrupted in GCs by the POP mixture, as demonstrated by lower oestradiol and progesterone secretion and greater lipid droplet accumulation. Furthermore, the POP mixture reduced GC viability and increased apoptosis, assessed using caspase-3 activity. The POP mixture significantly increased the number of oocytes that successfully progressed to the second meiotic metaphase and the oocyte reactive oxygen species (ROS) concentration. Conclusions. Thus, a mixture of POPs that are typically present in human FF has detrimental effects on ovarian function: it reduces the viability of GCs, and increases the oocyte concentrations of ROS. Implications. These results indicate that chronic exposure to POPs adversely affects female reproductive health.

show abstract

Persistent endocrine-disrupting chemicals found in human follicular fluid stimulate the proliferation of granulosa tumor spheroids via GPR30 and IGF1R but not via the classic estrogen receptors

Cited by 38 publications

References 41 publications

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Persistent organic pollutants affect steroidogenic and apoptotic activities in granulosa cells and reactive oxygen species concentrations in oocytes in the mouse

Contact Info

Product

Resources

About