Bisphenol A and bisphenol S both disrupt ovine granulosa cell steroidogenesis but through different molecular pathways

Têteau, Ophélie; Carvalho, Anais Vitorino; Papillier, Pascal; Mandon‐Pepin, Béatrice; Jouneau, Luc; Jarrier-Gaillard, Peggy; Desmarchais, Alice; Riviere, Marie-Emilie Lebachelier de la; Vignault, Claire; Maillard, Virginie; Binet, Aurélien; Uzbekova, Svetlana; Elis, Sébastien

doi:10.1186/s13048-023-01114-4

Cited by 16 publications

(5 citation statements)

References 84 publications

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“…While their impact on fertility is less well studied, initial reports indicate they also exhibit negative effects on reproductive functions, albeit through distinct intracellular pathways and mechanisms compared to BPA ( Rochester and Bolden, 2015 ; Abouhamzeh et al , 2023 ). In various animal models, BPS has been shown to disrupt granulosa cell steroidogenesis ( Téteau et al , 2020 , 2023 ), impair the in vitro early developmental competence of oocytes and embryos ( Desmarchais et al , 2020 ; Žalmanová et al , 2023 ) and reduce the motility of spermatozoa ( Torres-Badia et al , 2023 ; Téteau et al , 2023 ). Similarly, BPF has been shown to affect motility, capacitation, and mitochondrial membrane potential in cryopreserved bovine sperm ( Nguyen et al , 2022 ; Davis et al , 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Disposables used cumulatively in routine IVF procedures could display toxicity

Delaroche,

Besnard,

Ouary

et al. 2024

Human Reproduction

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STUDY QUESTION Is there a cumulative toxicity of disposables used in IVF procedures? SUMMARY ANSWER A toxicity may be detected when consumables are used cumulatively, while no toxicity is detected when the same consumables are used and tested individually. WHAT IS KNOWN ALREADY Many components of items used in IVF laboratories may impair human embryonic development. Consequently, it is necessary to screen all reagents and materials which could be in contact with gametes and embryos. Toxicity tests, such as the mouse embryo assay and the human sperm motility assay (HSMA), are used by manufacturers as quality control tools to demonstrate the safety of their products. This evaluation is currently individually performed for each single consumable. However, during an IVF cycle, several devices are used sequentially, potentially creating a cumulative exposure to chemical contaminants, which could not be detected for individually tested consumables. STUDY DESIGN, SIZE, DURATION The objective of this observational study conducted from March 2021 to October 2022 was to evaluate with the HSMA methodology if there was a cumulative toxicity when several disposables are sequentially used. Fourteen categories of consumables currently used in routine IVF procedures were studied, which included devices used for sperm and oocyte collection (cups, condoms, and oocyte aspiration needles), manipulation (flasks, tubes, tips, pipettes, embryo transfer catheters, syringes, and gloves), culture (dishes), and storage (straws). PARTICIPANTS/MATERIALS, SETTING, METHODS After obtaining patient consent, the surplus semen assessed as having normal parameters according to the World Health Organization 2010 criteria were used to perform the HSMAs. First, each consumable was tested individually. Then, associations of three, four, and five consumables, previously validated as non-toxic when tested individually, were analyzed. HSMAs were conducted three times to ensure reproducibility, with a defined toxicity threshold of a sperm motility index (SMI) below 0.85 in at least two of three tests. MAIN RESULTS AND THE ROLE OF CHANCE Thirty-six references of disposables were first individually tested across 53 lots. Forty-nine (92%) demonstrated compliance. However, four (8%) devices revealed toxicity: one lot of 1 ml syringes, two lots of sperm cups, and one lot of 25 cm2 flasks. These four references were excluded from the IVF routine procedures. A total of 48 combinations of consumables were assessed, involving 41 lots from 32 references that were previously individually tested. Among the evaluated combinations, 17 out of 48 (35%) associations exhibited toxicity with a SMI below 0.85 for two of the three tests (n = 8) or all the three tests (n = 9). Notably, three out of 17 (18%) of the three-consumable associations, five out of 16 (31%) of the four-consumable associations, and nine out of 15 (60%) of the five-consumable associations were found not compliant. The toxicity did not originate from a single consumable, because only consumables that were individually pre-validated as non-toxic were included in the combinations, but the toxicity had a cumulative origin. The risk of cumulative toxicity increased with the number of consumables included in the association (Cochran–Mantel–Haenszel statistic, P = 0.013). LIMITATIONS, REASONS FOR CAUTION The high proportion of non-compliant combinations of disposables can be attributed directly to the extreme rigorous extraction conditions employed during the tests, which could deviate from the conditions encountered in routine clinical use. Also, the methodology employed in the HSMAs (e.g. toxicity extraction duration, sperm concentrations, and protein supplementation of the medium) can influence the sensitivity of the tests. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the significance of performing toxicity testing on devices before introducing them into clinical practice. Disposables should be tested individually to detect immediate toxicities and also in combination. Our results advocate rationalizing the number of consumables used in each IVF procedure and re-evaluating the use of glass consumables. STUDY FUNDING/COMPETING INTEREST(S) This study received fundings from GCS Ramsay Santé pour l’Enseignement et la Recherche (Paris, France) and the Centre de Biologie Médicale BIOGROUP (Le Chesnay-Rocquencourt, France). The authors declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionmentioning

confidence: 99%

Disposables used cumulatively in routine IVF procedures could display toxicity

Delaroche,

Besnard,

Ouary

et al. 2024

Human Reproduction

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“…In their study, the tumorigenic phenotype in immunodeficient mice is displayed by exogenous expression of c-Fos in non-tumorigenic HNSCC MDA1386Tu cells. Overall, in non-tumorigenic cell lines, they have demonstrated that overexpression of c-Fos makes the cells tumorigenic and increases the expression of EMT/CSC marker genes [27]. A study by, Hearn et al, 2020 proposed the germline HSD3B1 genotype as a genetic biomarker of resistance to Androgen Deprivation Therapy (ADT) for prostate cancer [28].…”

Section: Discussionmentioning

confidence: 99%

Xenoestrogen and Its Interaction with Human Genes and Cellular Proteins: An In-Silico Study

Warrier,

VG,

R L

et al. 2024

Asian Pac J Cancer Prev

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Background: Breast cancer represents one of the leading causes of death worldwide. Apart from genetic factors, the sex hormone estrogen plays a pivotal role in breast cancer development. We are exposed to a plethora of estrogen mimics on a daily basis via various routes. Nevertheless, how xenoestrogens, the exogenous estrogen mimics, modulate cancer-associated signaling pathways and interact with specific genes is still underexplored. Hence, this study aims to explore the direct or indirect binding partners of xenoestrogens and their expression upon exposure to these estrogenic compounds. Methods: The collection of genes linked to the xenoestrogens Octylphenol, Nonylphenol, Bisphenol-A, and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane were gathered from the Comparative Toxicogenomics Database. Venny 2.1 was utilized to pinpoint the genes shared by these xenoestrogens. Subsequently, the shared genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resource. A xenoestrogen-protein interaction network was constructed using Search Tool for Interactions of Chemicals. The expressions of common genes were studied with the microarray dataset GSE5200 from the Gene Expression Omnibus database. Also, the expression of a common gene set within different breast cancer subtypes was identified using the University of California, Santa Cruz Xena. Results: The genes linked to xenoestrogens were identified, and 13 genes were found to interact with all four xenoestrogens. Through DAVID analysis, the genes chosen are found to be enriched for various functions and pathways, including pathways in cancer, chemical carcinogenesis-receptor activation, and estrogen signaling pathways. The results of the Comparative Toxicogenomics Database and the chemical-protein interaction network derived from STITCH were similar. Microarray data analysis showed significantly high expression of all 13 genes in another study, with Bisphenol-A and Nonylphenol treated MCF-7 cells, most of the genes are expressed in luminal A or basal breast cancer subtype. Conclusion: In summary, the genes associated with the four xenoestrogens were mostly linked to pathways related to tumorigenesis, and the expression of these genes was found to be higher in breast cancer.

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“…В світовій промисловості найбільшого поширення, із групи ендокринних руйнівників, набув Бісфенол А [5]. На теперішній час проведено ряд досліджень по виявленню патологічного впливу речовин з ендокринними властивостями на складні механізми сперматогенезу [6]. Дослідним шляхом доведено, що вплив високих доз ВРА викликав у чоловіків апоптоз клітин Лейдіга та ряд гістопатологічних змін в сім'яниках, включаючи редиціювання шарів сперматогенного епітелію, збільшення маси тіла, зменшення маси сім'яників та дисфункцію сперматогенезу, яка проявлялась значно пізніше після періоду впливу ВРА [7].…”

Section: постановка проблемиunclassified

“…Щури самців, які піддавалися дії BPA в період пренатального та постнатального розвитку, мали низьку масу сім'яників та низький рівень тестостерону у дорослому віці [8]. Загалом, складність репродуктивної функції робить її вразливою до негативного впливу найбільш поширеного з групи ендокринних дизрапторівбісфенолу А, зумовлює актуальність вивчення цієї медичної та соціальної проблеми, а розробка заходів прогнозування наслідків впливу, профілактики та лікування порушень репродуктивного здоров'я набуває особливої соціальної цінності при розробці моделі надання медичної допомоги чоловікам, які страждають на безпліддя [6].…”

Section: постановка проблемиunclassified

Зміна Маси Тіла Та Фізіологічного Стану Сім’яників Під Впливом Бісфенолу А

Ярошенко

2024

Перспективи та інновації науки

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The effect of bisphenol A (BPA) on the testes can cause a complex of pathological changes in the reproductive system; it is possible that bisphenol A triggers a cascade of pathological changes in the testes that negatively affect the reproductive ability of men. One of the main signs of the level of toxic damage to the body is a significant change in body weight. The aim of the study was to analyze the dynamics of changes in body weight and the physiological state of the testes under the influence of bisphenol A. during the experiment, in rats of experimental groups, body weight increased depending on the level of toxic exposure to BPA. Animals in groups F0-3 and F0-4 gained 23.6 and 28.9% more weight than rats in the control group. During the experiment, rats exposed to BPA at a dose of 250 mg/kg/day experienced a slowdown in rat testicular weight gain and a decrease in the gonado-somatic index compared to the testes of the control rats. In the middle of 27% of the convoluted seminal tubes that suffered severe damage to the spermatogenic epithelium, a cavity was formed with a violation of spermatogenesis processes. The spermatogenesis index at the end of the experiment decreased from 4.02±0.25 to 2.89±0.31 and 2.36±0.28, or by 28.11 and 41.29%, respectively, in groups F0-3 and F0-4 (p> 0.005).Disorders of spermatogenesis were also manifested by a decrease in the proportion of germ cells of the Sertoli cell population that was relatively stable to toxicant exposure. Thus, during the experiment, the relaxation index (spermatogenesis intensity) decreased from 19.20±1.54 to 17.07±0.39 and 16.07± 1.83 or by 11.19 and 16.30 %, respectively, in groups F0-3 and F0-4, compared with animals of the control group of rats F0-1 (p<0.005), which indicates a decrease in the functional ability of the testes of rats exposed to the pathological influence of BPA. In general, the data of physical development of experimental animals showed changes in the functional state of the body and were a significant marker for assessing the state of Health. the experimental data obtained show that BPA caused pathological changes in the structural elements of the testes, contributed to a decrease in the mass and size of the testes of rats of the F0-3 and F0-4 groups, compared with similar indicators of rats of the F0-1 group.

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Bisphenol A and bisphenol S both disrupt ovine granulosa cell steroidogenesis but through different molecular pathways

Cited by 16 publications

References 84 publications

Disposables used cumulatively in routine IVF procedures could display toxicity

Disposables used cumulatively in routine IVF procedures could display toxicity

Xenoestrogen and Its Interaction with Human Genes and Cellular Proteins: An In-Silico Study

Зміна Маси Тіла Та Фізіологічного Стану Сім’яників Під Впливом Бісфенолу А

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