Does BPA alter steroid hormone synthesis in human granulosa cells<i>in vitro</i>?

Mansur, Abdallah; Adir, Michal; Yerushalmi, Gil M.; Hourvitz, Ariel; Gitman, Hila; Yung, Yuval; Orvieto, Raoul; Machtinger, Ronit

doi:10.1093/humrep/dew088

Cited by 67 publications

(58 citation statements)

References 24 publications

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“…These disparities demonstrate that the effects of BPA cannot be extrapolated to make conclusions about BPS or other structurally related substitutes, and that thorough testing is required for each individual chemical. Previous studies have reported that μM concentrations of BPA reduce oestradiol production in rat and human granulosa cells (Mansur et al., ; Zhou et al., ). All of these studies also detected BPA‐mediated alterations in granulosa cell progesterone production, whereas no effects of BPS on progesterone production were found in the current study.…”

Section: Discussionmentioning

confidence: 94%

“…However, to the best of our knowledge, there is no information about whether BPS affects follicular cell function in mammals. BPA is well established to affect female fertility (Ziv-Gal & Flaws, 2016), including altering the function of granulosa cells (Mansur et al, 2016;Mlynarčíková, Kolena, Ficková, & Scsuková, 2005;Xu et al, 2002) and theca cells (Zhou, Liu, Liao, Han, & Liu, 2008) in a variety of species. Although BPS and BPA are structurally related, the two compounds exhibit different potencies for steroid hormone receptors (Rochester & Bolden, 2015) demonstrating that the effects of BPS on female reproduction cannot be inferred from what is known about BPA.…”

Section: Introductionmentioning

confidence: 99%

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The impact of bisphenol S on bovine granulosa and theca cells

Campen

Lavallée

Combelles

2018

Reprod Domestic Animals

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Bisphenol S (BPS) is an endocrine-disrupting chemical with multiple potential mechanisms of action, including as an oestrogen receptor agonist. BPS is increasingly used in plastics and thermal receipts as a substitute for bisphenol A, which has been phased out due to concerns about human health implications. The ability of BPS to alter female reproductive function in mammals has not been widely studied, despite the importance of normal hormone signalling for female reproduction. The aim of this study was to investigate how BPS (in a wide range of doses, including very low doses) affects granulosa cell and theca cell steroid hormone production and cell viability in the bovine. Granulosa cell oestradiol production was stimulated when cells were exposed to 100 μM BPS under basal conditions, but there was no effect of BPS when cells were stimulated with follicle-stimulating hormone (FSH). Additionally, there was no effect of BPS on granulosa cell progesterone production or cell viability under basal or FSH-stimulated conditions. BPS did not affect theca cell androstenedione or progesterone production, or theca cell viability under basal or luteinizing hormone-stimulated conditions. This study suggests for the first time that BPS may alter oestradiol production by bovine granulosa cells, albeit at a concentration that is unlikely to be physiologically relevant. Further studies are needed to determine the effects of BPS on the bovine oocyte and on other functions of follicular cells.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

The impact of bisphenol S on bovine granulosa and theca cells

Campen

Lavallée

Combelles

2018

Reprod Domestic Animals

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“…A number of studies have demonstrated that xenoestrogens can alter granulosa cell steroidogenesis. BPA lowers progesterone biosynthesis and reduces the mRNA levels of Hsd3b1, Cyp11a1 and Cyp19a1 in human granulosa cells (Mansur et al, 2016;Mansur et al, 2017),…”

Section: Discussionmentioning

confidence: 99%

Environmental mixture with estrogenic activity increases Hsd3b1 expression through estrogen receptors in immature rat granulosa cells

Nenadov

Pogrmić-Majkić

et al. 2018

J of Applied Toxicology

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Humans are exposed not only to single endocrine disruptors, but also to chemical mixtures that can adversely affect their reproductive health. Steroidogenesis in reproductive tissues is emerging as the key target of endocrine disruptor action. Here, we analyzed the effect of environmental chemical mixtures with estrogenic activity on steroidogenic processes in immature rat granulosa cells and whether the observed steroidogenic effects were mediated through estrogen receptors. Extracts from untreated wastewater were prepared by solid-phase extraction and silica gel fractionation. ER-CALUX assay showed that the polar fractions of wastewater exerted different levels of estrogenic activity. Exposure of immature granulosa cells to the polar fraction exerting 9 ng of 17β-estradiol equivalents per liter of water of estrogenic activity increased mRNA expression of the key enzymes of progesterone biosynthetic pathway Star and Hsd3b1, but did not alter the level of Cyp19a1 and Lhr. Addition of estrogen receptor inhibitor ICI 182 780 prevented the estrogenic mixture-induced increase in Hsd3b1, but not Star mRNA level in immature granulosa cells. These results indicate that the environmental chemical mixtures with estrogenic activity exert endocrine disrupting effects by augmenting the progesterone biosynthetic pathway in immature rat granulosa cells, which is an effect achieved in part through activation of the estrogen receptors.

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“…Previous studies with both animal and in vitro experiments with human luteinized ovarian granulosa cells have demonstrated the ability of bisphenol‐A (BPA) to alter the steroidogenesis in granulosa cells . However most studies to date have not yet elucidated the indirect impact of BPA resulting from maternal exposure, on granulosa cell estrogen biosynthesis in parallel with functionally associated miRNA expression, especially during the reproductively active life of the exposed organism.…”

Section: Introductionmentioning

confidence: 94%

Prenatal exposure to bisphenol‐A altered miRNA‐224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F₁ adult offspring

Lite

Ahmed

Santosh

et al. 2019

J Biochem & Molecular Tox

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This study was aimed to predict bisphenol-A (BPA)-responsive miRNA's using an in silico approach and to study their expression in granulosa cells of animals exposed prenatally to BPA. Pregnant Wistar rats were exposed to BPA through water (25 μg/L, 250 μg/L, and 2.5 mg/L) during gestation. The expression of miRNA-133b, miRNA-378 and miRNA-224 were analyzed in ovarian granulosa cells. BPA affected the postnatal developmental landmarks such as weight of the pups at birth and reduced anogenital distance. BPA exposed animals showed elevated serum estradiol (E2) levels, while follicle-stimulating hormone levels were reduced. The expression of miRNA-224 and aromatase protein levels were found to be increased. This preliminary finding reveals the impact of early life exposure to BPA on the long-term ovarian functions that may be mediated through miRNA-based granulosa cell response. Besides, it is also a compelling indicator for the subclinical response that could have important consequences on female fertility.

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Does BPA alter steroid hormone synthesis in human granulosa cellsin vitro?

Abstract: This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest.

Cited by 67 publications

References 24 publications

The impact of bisphenol S on bovine granulosa and theca cells

The impact of bisphenol S on bovine granulosa and theca cells

Environmental mixture with estrogenic activity increases Hsd3b1 expression through estrogen receptors in immature rat granulosa cells

Prenatal exposure to bisphenol‐A altered miRNA‐224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F₁ adult offspring

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Does BPA alter steroid hormone synthesis in human granulosa cellsin vitro?

Abstract: This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest.

Cited by 67 publications

References 24 publications

The impact of bisphenol S on bovine granulosa and theca cells

The impact of bisphenol S on bovine granulosa and theca cells

Environmental mixture with estrogenic activity increases Hsd3b1 expression through estrogen receptors in immature rat granulosa cells

Prenatal exposure to bisphenol‐A altered miRNA‐224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F1 adult offspring

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Prenatal exposure to bisphenol‐A altered miRNA‐224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F₁ adult offspring