Comparative in vivo and in vitro analysis of possible estrogenic effects of perfluorooctanoic acid

Yao, Pei-Li; Ehresman, David J.; Rae, Jessica; Chang, Shu Ching; Frame, Steven R.; Butenhoff, John L.; Kennedy, Gerald L.; Peters, Jeffrey M.

doi:10.1016/j.tox.2014.10.008

Cited by 21 publications

(10 citation statements)

References 42 publications

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“…Expression and localization of PCNA and OCT3/4 in ectopic xenograft tumors were determined by immunohistochemistry using 3,3′-diaminobenzidine (DAB) as a substrate and counterstained by hematoxylin as previously described [ 49 ]. Twenty fields per sections and two sections per tumor sample were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms

et al. 2015

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Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has important physiological functions in control of cell growth, lipid and glucose homeostasis, differentiation and inflammation. To investigate the role of PPARβ/δ in cancer, stable human testicular embryonal carcinoma cell lines were developed that constitutively express PPARβ/δ. Expression of PPARβ/δ caused enhanced activation of the receptor, and this significantly decreased proliferation, migration, invasion, anchorage-independent growth, and also reduced tumor mass and volume of ectopic xenografts derived from NT2/D1 cells compared to controls. The changes observed in xenografts were associated with decreased PPARβ/δ-dependent expression of proliferating cell nuclear antigen and octamer-binding transcription factor-3/4, suggesting suppressed tumor proliferation and induction of differentiation. Inhibition of migration and invasion was mediated by PPARβ/δ competing with formation of the retinoic acid receptor (RAR)/retinoid X receptor (RXR) complex, resulting in attenuation of RARα-dependent matrix metalloproteinase-2 expression and activity. These results demonstrate that PPARβ/δ mediates attenuation of human testicular embryonal carcinoma cell progression through a novel RAR-dependent mechanism and suggest that activation of PPARβ/δ inhibits RAR/RXR dimerization and represents a new therapeutic strategy.

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Section: Methodsmentioning

confidence: 99%

Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms

et al. 2015

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“…PFAS are also known to have weak oestrogenic activity and, as with other weak oestrogens, exposure to a combination of E2, and these compounds produced anti-estrogenic effects ( Liu et al , 2007 ). Studies have reported contradictory results using in vitro screening systems to assay for hormone activity by ER- or AR-mediated transactivation in the human breast adenocarcinoma cell lines MCF-7 and MVLN ( Maras et al , 2006 ; Wang et al , 2012 ; Kjeldsen and Bonefeld-Jørgensen, 2013 ; Behr et al , 2018 ), human adrenal carcinoma cell H295R ( Du et al , 2013a ; 2013b ; Wang et al , 2015 ; Behr et al , 2018 ) and human placental choriocarcinoma cell JEG-3 ( Gorrochategui et al , 2014 ), as well as in in vivo testing ( Biegel et al , 1995 ; Du et al , 2013a ; Yao et al , 2014 ). It remains unclear whether PFAS affect oestrogen or androgen receptor signalling at concentrations relevant to human exposure.…”

Section: Mechanistic Evidence For Ovarian Toxicity Of Pfasmentioning

confidence: 99%

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

Ding

Harlow

Randolph

et al. 2020

Human Reproduction Update

211

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BACKGROUND Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women’s health. OBJECTIVE AND RATIONALE This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function. SEARCH METHODS A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors’ knowledge of the topic and key terms. OUTCOMES Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood–follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus. WIDER IMPLICATIONS The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality.

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“…Importantly, phytoestrogens are described to influence the fertility and puberty in female and male mice [4][5][6][7][8][9] which might have an impact on the production of embryos, especially when superovulating female donors [10,11]. A possible estrogenic effect can be determined by calculating the relative uterus weight using a uterotrophic bioassay [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

The role of diet and housing-temperature in the production of genetically modified mouse embryos and their developmental capacity after cryopreservation

2015

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Comparative in vivo and in vitro analysis of possible estrogenic effects of perfluorooctanoic acid

Cited by 21 publications

References 42 publications

Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms

Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

The role of diet and housing-temperature in the production of genetically modified mouse embryos and their developmental capacity after cryopreservation

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