Di(2-ethylhexyl) phthalate (DEHP) increases proliferation of epithelial breast cancer cells through progesterone receptor dysregulation

Crobeddu, Bélinda; Ferraris, Emanuelle; Kolasa, Élise; Plante, Isabelle

doi:10.1016/j.envres.2019.03.037

Cited by 70 publications

(30 citation statements)

References 72 publications

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“…Perinatal exposure of female rats to diisononyl phthalate (20,000 ppm) lowered PR mRNAs levels in the medial preoptic area (Takagi et al 2005). A significant increase in the nuclear levels of PR was observed in epithelial breast cancer cells exposed to 10 lM DEHP (Crobeddu et al 2019). Besides its function in female reproduction, the PR has been shown to play a key role in neuroprotection and promyelination (González et al 2020;Schumacher et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms

Adam

Brusamonti

Mhaouty-Kodja

2021

Environ Health Perspect

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BACKGROUND:We have previously shown that adult male mice exposure to low doses of an ubiquitous endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP), alters courtship behavior. OBJECTIVE: The effects of adult exposure to low doses of DEHP alone or in an environmental phthalate mixture on estrous cyclicity, reproductive behavior, and underlying neural structures were analyzed in female mice. METHODS: Two-month-old C57BL/6J females were exposed orally for 6 wk to DEHP alone (0, 5 or 50 lg=kg=d) or to DEHP (5 lg=kg=d) in a phthalate mixture. Estrous cyclicity was analyzed in intact mice, and behavior [lordosis, olfactory preference, partner preference, ability to stimulate male ultrasonic vocalizations (USVs)] was measured in ovariectomized mice primed with estradiol and progesterone. Immunohistochemical studies were conducted in the neural structures involved in behavior for estrogen receptor (ER) a and progesterone receptor (PR). RESULTS: Exposure to DEHP alone or in mixture lengthened the estrous cycle duration, with a shorter proestrus and longer estrus and metestrus stages. Under normalized hormonal levels, females exposed to DEHP alone or in mixture exhibited altered olfactory preference. A lower lordosis behavior and ability to attract and stimulate male emission of courtship USVs was observed, probably due to modifications of pheromonal emission in exposed females. The behavioral alterations were associated with a lower number of PR-expressing neurons, without changes in ERa, in the neural circuitry underlying sexual behavior. The majority of effects observed was comparable between the two DEHP doses and were driven by DEHP in the mixture. CONCLUSIONS: Exposure to environmental doses of DEHP alone or in mixture altered several components of female sexual behavior in mice, probably through selective disruption of neural PR signaling. Together with the previously reported vulnerability of male mice, this finding suggests a major impact of exposure to phthalates on sexual reproduction, including in other species with similar neural regulatory processes.

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Section: Discussionmentioning

confidence: 99%

Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms

Adam

Brusamonti

Mhaouty-Kodja

2021

Environ Health Perspect

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“…In T-47D breast cancer cells, DEHP and MEHP induced the PRα expression and nuclear localization. Phthalate treatment caused T-47D cell proliferation without apoptosis (Crobeddu et al, 2019). On the other hand, DEHP enhanced ERα-mediated transcriptional activity and decreased ERα protein levels in hypoxic in MCF-7 breast cancer cells (Park et al, 2019).…”

Section: Suggested Effects Of Phthalates On Health As Endocrine Disrumentioning

confidence: 96%

Di-(2-ethylhexyl) Phthalate (DEHP) and Uterine Histological Characteristics

Cheon¹

2020

Dev. Reprod.

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Phthalates have a long industrial history. It is suspected that phthalates and their metabolites have detrimental effects on reproduction and development. They are well-known for their anti-androgenic effects. Several studies have indicated that phthalates and their metabolites are reprotoxic in males and endocrine disruptors. Reproduction and embryogenesis occur in the uterus of female eutherian mammals. A horizontal analytical method is preferred to elucidate the toxic effects of phthalates on human reproduction. Nevertheless, there are vast numbers of known phthalates and not all of their modes of action have been clarified. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer and has been the subject of numerous toxicological studies. However, few of these have reported on the toxic effects of DEHP, its metabolites, other phthalates, or mixtures on female reproduction. Acute and high doses of DEHP adversely affect uterine histology. Recently, it was disclosed that chronic exposures to low doses of DEHP have endocrine disruption efficacy. DEHP induces various cellular responses including modulation of the expression and regulation of steroid hormone receptors and transcription and paracrine factors. Uteri do not respond uniformly to DEHP exposure. The phenotypic manifestations and effects on fertility in response to DEHP and its metabolites may vary with species, developmental stage, and generation. Hence, DEHP exposure may histological alter the uterus and induce endometriosis, endometriosis, hyperplasia, myoma, and developmental and reproductive toxicity.

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“…Li et al, 2019 reported that maternal prenatal exposure to phenols (2,4-dichlorophenol and 2,5-dichlorophenol) is inversely correlated with male birth weight and exposure to phthalates is associated with preterm birth or pregnancy loss [24] . According to Crobeddu et al, 2019 phthalates family (used for industrial plasticizers to impart flexibility and durability to polyvinyl chloride) is generally considered as an endocrine disruptor could potentially increase the risks to develop breast cancer [25] . A Missouri jury ordered Johnson & Johnson to pay $72 million to the family of Jacqueline Fox, whose death by ovarian cancer was linked to her daily use of talcum-based Johnson's Baby Powder and Shower to Shower products [26] .…”

Section: Introductionmentioning

confidence: 99%

Cosmetics’ Safety: Gray Areas with Darker Inside

Mohiuddin

Road²

2019

Journal of Dermatological Research

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Cosmetics and personal care products are ubiquitous. Currently, an increasing number of compounds are being assimilated in the and to various types of chemicals, got from a few sources, may cause the alleged "cocktail effect" because of the synergistic interaction of various substances and, likewise, the "added substance effect" in light of the nearness of a similar ingredient in numerous items. Actually, every one of the ingredients utilized in cosmetic items meet certain regulatory prerequisites. Notwithstanding, the utilization of numerous substances is permitted inside specific limits, because of their toxicity at higher concentrations.

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Di(2-ethylhexyl) phthalate (DEHP) increases proliferation of epithelial breast cancer cells through progesterone receptor dysregulation

Cited by 70 publications

References 72 publications

Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms

Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms

Di-(2-ethylhexyl) Phthalate (DEHP) and Uterine Histological Characteristics

Cosmetics’ Safety: Gray Areas with Darker Inside

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