BPA and its analogs increase oxidative stress levels in in vitro cultured granulosa cells by altering anti-oxidant enzymes expression

Sabry, Reem; Nguyen, Minh-Khai; Younes, Sonia Ben; Favetta, Laura A.

doi:10.1016/j.mce.2022.111574

Cited by 15 publications

(10 citation statements)

References 55 publications

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“…Transfected cells were treated with BPA at the current reported LOAEL dose of 0.05 mg/mL [ 24 , 27 ]. In addition to BPA, cells were also treated with an ethanol vehicle in which BPA is dissolved.…”

Section: Resultsmentioning

confidence: 99%

“…Once the transfection conditions were determined, transfected cells were treated with a vehicle (0.1% ethanol) or BPA (0.05 mg/mL in 0.1% ethanol) in OptiMEM for 12 h then frozen in liquid nitrogen and stored at −80 °C for RNA and protein analysis. This dose of BPA is the currently reported LOAEL dose, which was previously determined to be a physiologically and environmentally relevant dose in bovine reproduction [ 24 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

“…It has been detected in oocytes, granulosa cells, and embryos with negative correlations to oocyte competence and embryo development. In bovine oocytes, granulosa cells, and early embryos, BPA has been shown to induce oxidative stress, alter sex ratios, disrupt gap junctions, and extensively dysregulate gene expression [ 24 , 25 , 26 , 27 ]. BPA has been shown to affect epigenetics, such as DNA methylation and histone modification, in part, by disrupting the activity of methyltransferase and acetylase enzymes [ 8 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Sabry

Williams

Werry

et al. 2022

IJMS

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microRNAs (miRNAs) are susceptible to environmental factors that might affect cellular function and impose negative effects on female reproduction. miR-21 is the most abundant miRNA in bovine granulosa cells and is widely reported as affected by Bisphenol A (BPA) exposure, yet the cause and consequences are not entirely elucidated. BPA is a synthetic endocrine disruptor associated with poor fertility. miR-21 function in bovine granulosa cells is investigated utilizing locked nucleic acid (LNA) oligonucleotides to suppress miR-21. Before measuring apoptosis and quantifying miR-21 apoptotic targets PDCD4 and PTEN, transfection was optimized and validated. BPA was introduced to see how it affects miR-21 regulation and which BPA-mediated effects are influenced by miR-21. miR-21 knockdown and specificity against additional miRNAs were confirmed. miR-21 was found to have antiapoptotic effects, which could be explained by its effect on the proapoptotic target PDCD4, but not PTEN. Previous findings of miR-21 overexpression were validated using BPA treatments, and the temporal influence of BPA on miR-21 levels was addressed. Finally, BPA effects on upstream regulators, such as VMP1 and STAT3, explain the BPA-dependent upregulation of miR-21 expression. Overall, this research enhances our understanding of miR-21 function in granulosa cells and the mechanisms of BPA-induced reproductive impairment.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Sabry

Williams

Werry

et al. 2022

IJMS

Self Cite

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“…BPA acts as a xenoestrogen that is capable of binding to various receptors such as estrogen receptor alpha and beta (ERa and ERb), eliciting endocrine disrupting effects (9). BPA has been associated with female reproductive damage via delayed oocyte maturation, diminished ovarian reserve, increases in follicular atresia, increases in oxidative stress, changes in gene expression, and overall reduction in developmental capabilities to produce a healthy offspring (10)(11)(12)(13)(14). Due to the negative health outcomes associated with BPA, many countries have taken steps toward replacing BPA with alternatives, including its structural analogs, bisphenol S (BPS) and bisphenol F (BPF), despite limited knowledge available regarding their effects on health and a great chance that they would also share comparable physiological and toxicological effects considering their structural similarities (15).…”

Section: Introductionmentioning

confidence: 99%

Bisphenols A and F, but not S, induce apoptosis in bovine granulosa cells via the intrinsic mitochondrial pathway

Kourmaeva

Sabry²,

Favetta³

2022

Front. Endocrinol.

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With the gradual decline in global fertility rates, there is a need to identify potential contributing factors, their mechanisms of actions and investigate possible solutions to reverse the trend. Endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), are environmental toxicants that are known to negatively impact reproductive functions. As such, the use of BPA in the manufacturing industry has slowly been replaced by analogs, including bisphenol S (BPS) and bisphenol F (BPF), despite limited knowledge available regarding their impact on health and their safety. The following study investigates the effects of BPA, BPS and BPF at a concentration of 0.5 μg/mL and 50 μg/mL on bovine granulosa cell apoptosis, with the ultimate goal of determining how they may impact oocyte competence and, thus, overall fertility. The underlying hypothesis is that bisphenols disrupt the granulosa cell environment surrounding the oocyte inducing excessive apoptosis via the intrinsic mitochondrial pathway. To test this hypothesis, apoptosis was measured following a time- and dose-dependent exposure to all three bisphenols by flowcytometry paired with annexin V/PI staining as well as by quantification of key genes belonging to the intrinsic apoptotic pathway both at the mRNA and protein levels. The results of this study report that BPA and BPF reduce cell viability through reduced cell counts and increased apoptosis. This increase is due, in part, to the induction of apoptotic genes of the intrinsic pathway of apoptosis. Additionally, this study also suggests that BPS may not act on the intrinsic mitochondrial apoptotic pathway in bovine granulosa cells. Overall, this study allows us to establish potential apoptotic pathways activated by bisphenols as well as compare the relative apoptotic activities of BPA to its most widespread analogs.

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“…Previous studies have shown that BPA exposure damaged female estrus and disrupted redox balance, while the mechanism and antidote remained unclear. [10,13,22] Therefore, this study explored the mechanism of BPA-induced impairment on female estrous cycle and found Res, an effective antidote, could alleviate BPA-induced impairment, which provided a new way for the treatment of BPA-induced female reproductive disorders.…”

mentioning

confidence: 99%

Resveratrol improves estrus disorder induced by bisphenol A through attenuating oxidative stress, autophagy, and apoptosis

Jiao

Gao

Yong

et al. 2022

J Biochem & Molecular Tox

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Bisphenol A (BPA), as a widely used plasticizer, is easily absorbed by animals and humans. It has certain toxic effects on various tissues, including liver, heart, kidney, testis, and ovary. The toxic effects of BPA on animal reproduction have aroused widespread concern, but its regulatory mechanism and antidote in female animals estrus cycle remain unclear. In this study, the results displayed that BPA destroyed the normal estrus cycle of mice through decreasing the levels of progesterone and estradiol. Furthermore, BPA significantly increased the levels of oxidative stress, autophagy, and apoptosis in ovaries and granulosa cells. Interestingly, we found that the natural antioxidant resveratrol rescued estrus disorder and impaired estradiol secretion, reduced the abnormal reactive oxygen species accumulation, autophagy, and apoptosis in BPA exposed ovarian tissues. Moreover, transmission electron microscopy showed that resveratrol reduced BPA‐induced autophagic vesicles formation and flow cytometry showed that resveratrol inhibited the increase of apoptotic cells induced by BPA on granulosa cells. Therefore, the supplement of resveratrol could restore BPA‐induced estrus disorder by protecting ovarian granulosa cells. Overall, resveratrol is a potential drug to alleviate BPA‐induced estrous cycle disorders and ovarian damage.

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BPA and its analogs increase oxidative stress levels in in vitro cultured granulosa cells by altering anti-oxidant enzymes expression

Cited by 15 publications

References 55 publications

BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Bisphenols A and F, but not S, induce apoptosis in bovine granulosa cells via the intrinsic mitochondrial pathway

Resveratrol improves estrus disorder induced by bisphenol A through attenuating oxidative stress, autophagy, and apoptosis

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