Foetal exposure to the bisphenols BADGE and BPAF impairs meiosis through DNA oxidation in mouse ovaries

Abdallah, Sonia; Jampy, Amandine; Moison, Delphine; Wieckowski, Margaux; Messiaen, Sébastien; Martini, Emmanuelle; Campalans, Anna; Radicella, J. Pablo; Rouiller-Fabre, Virginie; Livera, Gabriel; Guerquin, Marie-Justine

doi:10.1016/j.envpol.2022.120791

Cited by 13 publications

(12 citation statements)

References 81 publications

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“…Moreover, in the present study, although we demonstrate that curcumin exerts protect effect by inhibiting Erk and p38 pathways, 66 EECs might still exhibit apoptosis through other signaling. Previous studies have shown that BPAF induces autophagy in rat testis 40 . Furthermore, the activation of autophagy contributes to ferroptosis, and the Nrf2 pathway also plays a key role in ferroptosis 67 .…”

Section: Discussionmentioning

confidence: 88%

“…To the best of our knowledge, this is the first study indicate that curcumin has protective properties against BPAF‐induced apoptosis. This may implicate that curcumin also has protective effect on other damaged cells caused by BPAF, such as BPAF‐induced testicular injury 38 and DNA oxidation in ovaries 40 . In addition, endoplasmic reticulum pathway has also been shown to activate the apoptosis pathway, leading to apoptosis 41 .…”

Section: Discussionmentioning

confidence: 98%

“…This may implicate that curcumin also has protective effect on other damaged cells caused by BPAF, such as BPAF-induced testicular injury 38 and DNA oxidation in ovaries. 40 In addition, endoplasmic reticulum pathway has also been shown to activate the apoptosis pathway, leading to apoptosis. 41 Studies have shown that curcumin can relieve zearalenone-induced apoptosis through endoplasmic reticulum stress.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that BPAF induces autophagy in rat testis. 40 Furthermore, the activation of autophagy contributes to ferroptosis, and the Nrf2 pathway also plays a key role in ferroptosis. 67 Thus, we inferred that BPAF might also regulate cell death through autophagy and ferroptosis, and the role of curcumin in this process also needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

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Curcumin alleviates bisphenol AF‐induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway

Liu

Wang

et al. 2023

Environmental Toxicology

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Bisphenol AF (BPAF), a BPA‐substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl‐2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH‐Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF‐induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen‐activated protein kinase (MAPK) pathway and nuclear factor‐erythroid 2‐related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF‐induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Curcumin alleviates bisphenol AF‐induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway

Liu

Wang

et al. 2023

Environmental Toxicology

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“…Only short term studies suggested that fetal germ cell differentiation could be impaired by EDC exposure. Among EDCs studied, bisphenols and phthalates were shown to impair PGC differentiation and induce germ cell apoptosis and cytokinesis impairment (Eladak et al, 2018; Li et al, 2022; Abdallah et al, 2023; Kilcoyne and Mitchell, 2019). The most widely used phthalate ester is di-(2-ethylhexyl) phthalate (DEHP), which is incorporated in plasticizers and other products (Li et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

Nicolas,

Moison,

Jampy

et al. 2023

Preprint

Self Cite

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Testicular cancer is an increasing burden in modern societies and the most common malignancy among young adult males. Environment contaminants, especially endocrine disrupting compounds (EDC), may play a significant role in the development of these cancers through epigenetic alterations occurring during fetal and neonatal development. As long-term studies in humans and suitable experimental models with the potential to develop testicular cancer are lacking, no causal link can be established between endocrine disruptor exposure and testicular cancer incidence. Therefore, we developed an experimental model that recapitulates the differentiation of germ cells from primordial germ cells (pluripotency) into spermatocytes (meiosis) by using xenografted human fetal testis combined with germ cell transplantation into adult testis compartments. Using this model, we demonstrate that long-term fetal exposure (until 12 weeks) to a mixture of Di-2-ethylhexylphthalate (DEHP) and Bisphenol A (BPA), two most prevalent plasticizers, could interfere with fetal germ cell differentiation, leading to carcinogenesis and seminomas. Transcriptome, methylome, and histological analyses reveal that BPA/DEHP exposure induced some significant hallmarks of germ cell tumors to occur: persistent pluripotent and proliferative germ cells, global hypomethylation of CpGs in germ cells, abnormal expression of meiotic markers and fibrotic signatures in fetal testis. Additionally, we found that EDC-exposed fetal germ cells were more likely to develop seminoma in a context that allows spermatogenesis to begin. This study proposes the first experimental evidence that EDC exposure can cause long-term, irreversible lesions in fetal germ cells, which then lead to testicular tumorigenesis in adults.

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Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression

Cao,

Xu,

Liu

et al. 2023

Environ Sci Pollut Res

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Growing evidence suggests that exposure of Bisphenol A (BPA), an endocrine disruptor that commonly presence in the environment, can impair reproduction. However, con icting results have been reported and the underling mechanism have not been fully understood. In this study, 3 weeks old male mice were exposed to 50mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm were counted, and the morphology was analyzed by PNA and pap staining. Fertilization capacity and successful rate was analyzed after mating with wide type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain and TUNEL assay. RNA-seq analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization e ciency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that at least partially due to epigenetic modi cation.

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Foetal exposure to the bisphenols BADGE and BPAF impairs meiosis through DNA oxidation in mouse ovaries

Cited by 13 publications

References 81 publications

Curcumin alleviates bisphenol AF‐induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway

Curcumin alleviates bisphenol AF‐induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression

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