Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells†

Chu, Pao-Hsien; Yang, Zemin; Huang, Hui-Hsin; Chang, Ai-An; Cheng, Yu‐Chen; Wu, Gwo-Jang; Lan, Hsin‐Chieh

doi:10.1093/biolre/iox162

Cited by 44 publications

(28 citation statements)

References 39 publications

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“…In metaphase II oocyte from in vitro-grown preantral follicles, 4.5 and 45 µM BPA reduced MAPK3 phosphorylation [51]. However, low doses of BPA (under 1µM) activates rapidly MAPK3/1 signalling in human placental and ovarian cancer cells [71,72]. Nevertheless, as we could not evidence the expected increase in MAPK3/1 phosphorylation between the 0 h control and 6 h IVM control conditions, and caution is needed to interpret these data.…”

Section: Bps Mechanism Of Actionmentioning

confidence: 64%

Bisphenol S Impaired In Vitro Ovine Early Developmental Oocyte Competence

Desmarchais

Têteau

Papillier

et al. 2020

IJMS

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Introduction: Bisphenol A (BPA) is a widespread compound in the plastic industry that is especially used to produce baby bottles, food packaging and metal cans. BPA, an endocrine disruptor, leads to alterations in reproductive function and therefore has been banned from the food industry. Unregulated BPA analogues, particularly Bisphenol S (BPS), have emerged and are now used in the plastic industry. Thus, this study aimed to examine the acute effects of low and environmental doses of BPS on ewe oocyte quality and developmental competence, and its mechanism of action, during in vitro maturation. Methods: Ewe cumulus-oocyte complexes underwent in vitro maturation in the presence or absence of BPS (1 nM, 10 nM, 100 nM, 1 µM or 10 µM). Oocytes were then subjected to in vitro fertilisation and development. Results: 1 µM BPS induced a 12.7% decrease in the cleavage rate (p = 0.004) and a 42.6% decrease in the blastocyst rate (p = 0.017) compared to control. The blastocyst rate reduction was also observed with 10 nM BPS. Furthermore, 10 µM BPS reduced the oocyte maturation rate, and 1 µM BPS decreased cumulus cell progesterone secretion. PR and AMH gene expression were reduced in cumulus cells. BPS induced a 5-fold increase in MAPK 3/1 activation (p = 0.04). Conclusions: BPS impaired ewe oocyte developmental competence. The data suggest that BPS might not be a safe BPA analogue. Further studies are required to elucidate its detailed mechanism of action.

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Section: Bps Mechanism Of Actionmentioning

confidence: 64%

Bisphenol S Impaired In Vitro Ovine Early Developmental Oocyte Competence

Desmarchais

Têteau

Papillier

et al. 2020

IJMS

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“…We also examined the MAPK3/1 signalling pathway. BPA reportedly exerts its effects at least partially through an increase in MAPK3/1 phosphorylation [52,53]. There was a transient increase in MAPK3/1 phosphorylation in both control and BPS-treated HGC.…”

Section: Bps Mechanisms Of Actionmentioning

confidence: 94%

Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro

Amar

Binet

Têteau

et al. 2020

IJMS

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Bisphenol S (BPS) is a structural analog of the endocrine disruptor bisphenol A (BPA); it is the main BPA replacement in the plastics industry. Previous studies have shown that BPA and BPS exhibit similar effects on reproduction in fish and rodent species. BPS reportedly alters steroidogenesis in bovine granulosa cells. Luteinised granulosa cells collected from 59 women who were undergoing an in vitro fertilization procedure were cultured for 48 h in the presence or absence of BPS (10 nM, 100 nM, 1 µM, 10 µM or 50 µM). BPS exposure was investigated by assessing follicular fluids from these 59 women for their BPS content. Culture medium, cells, total messenger RNA (mRNA) and total protein extracted from the luteinised granulosa cells were examined for oestradiol and progesterone secretion, cellular proliferation, viability, gene expression, steroidogenic enzyme expression and cell signaling. BPS was measured in follicular fluids using mass spectrometry. Exposure of granulosa cells to 10 or 50 µM BPS for 48 h induced a 16% (p = 0.0059) and 64% (p < 0.0001) decrease, respectively, in progesterone secretion; 50 µM BPS decreased oestradiol secretion by 46% (p < 0.0001). Ten µM BPS also tended to reduce CYP11A1 protein expression by 37% (p = 0.0947) without affecting HSD3B1 and CYP19A1 expression. Fifty µM BPS increased ERRγ expression. Environmental levels of BPS (nanomolar range) did not induce changes in steroidogenesis in human granulosa cells. The effects of BPS were observed after only 48 h of BPS exposure. These acute effects might be similar to chronic effects of physiological BPS levels.

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“…However, some experiments have shown that BPA increased the levels of anti-apoptotic proteins like Bcl-2 and Hsp70, and decreased HIF-1α levels in BeWo cells, reducing apoptosis [46]. Furthermore, a low dose of BPA (1-1000 nM) could activate the ERK signaling pathway to downregulate the expression of CYP11A1 and CYP19, decrease placental aromatase activity, and cause the estradiol and progesterone production to decrease [47]. A lack of hormones may contribute to placental insufficiency and pregnancy failure.…”

Section: Bisphenol Amentioning

confidence: 99%

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

Tang

Deng

et al. 2020

IJMS

122

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Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.

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Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells†

Cited by 44 publications

References 39 publications

Bisphenol S Impaired In Vitro Ovine Early Developmental Oocyte Competence

Bisphenol S Impaired In Vitro Ovine Early Developmental Oocyte Competence

Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

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