The effects of low doses of bisphenol A on the morphology of oocytes in Wistar female rats exposed in vivo.
- Authors: Grybachyova N.1, Soliannikova D.1, Brukhin G.1
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Affiliations:
- FSBEI HE «South-Ural State Medical University» MOH Russia
- Section: Original research
- Published: 02.10.2025
- URL: https://journals.eco-vector.com/MAJ/article/view/654041
- DOI: https://doi.org/10.17816/MAJ654041
- ID: 654041
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Abstract
Introduction: The effect of bisphenol A on the maturation and quality of female gametes has been studied in a large number of papers by different authors. However, the main conclusions about the influence of this endocrine disruptor concerned disorders in oocyte maturation and chromosome segregation during meiosis, impaired distribution and functions of organelles, as well as dysfunctions of cumulus cells. At the same time, studies of the impact of bisphenol A on the morphology of human or animal oocytes are limited to data about the maturity of female gametes and do not study the features of intracytoplasmic and extracytoplasmic changes.
Aim of the research: analysis of morphological features of oocytes from mature Wistar rats under chronic exposure to low doses of bisphenol A in vivo.
Material and methods: Laboratory animals were divided into the experimental group consisting of animals receiving bisphenol A per os at a dose of 25 μg/kg bw daily for 45 days before oocyte collection (n=9, oocytes` number =74) and the control group including intact female rats (n=11, oocytes` number =105). The total relative content of all abnormal oocytes in each group, as well as the ratio of various forms of oocytes` dysmorphisms were analyzed.
Results: In the experimental group of animals, female gametes with intracytoplasmic disorders of morphology (peripheral granulation of the ooplasm), anomalies of the first polar body (increased size and fragmentation), morphological changes of zona pellucida and an increase of the perivitelline space were more common. The total relative content of oocytes with different dysmorphisms in animals of the experimental group was higher than in the control group.
Conclusion: Bisphenol A at a dose of 25 μg/kg bw administered orally daily for 45 days leads to the following changes in the morphology of mature Wistar rats` oocytes: an increase in the number of oocytes with peripheral granulation, giant first polar body and its fragmentation, anomalies of zona pellucida and an increase in the perivitelline space, as well as an increase in the total content of oocytes carrying a particular dysmorphism. Thus, the wide range of dysmorphisms observed in female gametes of rats that ovulated in the natural estrous cycle is the result of several potential mechanisms of the effect of bisphenol A on their growth and maturation.
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About the authors
Natalya Grybachyova
FSBEI HE «South-Ural State Medical University» MOH Russia
Author for correspondence.
Email: natalya.v_microbiolog@mail.ru
ORCID iD: 0009-0006-1527-5500
Postgraduate (Biology) of Department of histology, embryology and cytology, FSBEI HE SUSMU MOH Russia
Russian FederationDarya Soliannikova
Email: ZhdanovaDR@mail.ru
Gennadij Brukhin
Email: BGenVas@mail.ru
References
- Eladak S, Grisin T, Moison D, et al. A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertility and Sterility. 2015;103(1):11 – 21. https://doi.org/10.1016/j.fertnstert.2014.11.005
- Ikezuki Y, Tsutsumi O, Takai Y, et al. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Human Reproduction. 2002;17(11):2839 – 2841. https://doi.org/10.1093/humrep/17.11.2839
- Kaddar N, Bendridi N, Harthé C, et al. Development of a radioimmunoassay for the measurement of Bisphenol A in biological samples. Analytica Chimica Acta. 2009;645(1-2): 1–4. https://doi.org/10.1016/j.aca.2009.04.036
- Poormoosavi SM, Behmanesh MA, Janati S, Najafzadehvarzi H. Level of Bisphenol A in Follicular Fluid and Serum and Oocyte Morphology in Patients Undergoing IVF Treatment. Journal of Family and Reproductive Health. 2019;13(3):154-159.
- https://doi.org/10.18502/jfrh.v13i3.2129
- Eichenlaub-Ritter U, Pacchierotti F. Bisphenol A Effects on Mammalian Oogenesis and Epigenetic Integrity of Oocytes: A Case Study Exploring Risks of Endocrine Disrupting Chemicals. BioMed Research International. 2015: 1–11. https://doi.org/10.1155/2015/698795
- Pacchierotti F, Ranaldi R, Eichenlaub-Ritter U, et al. Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse. Genetic Toxicology and Environmental Mutagenesis. 2008;651(1-2): 64–70. https://doi.org/10.1016/j.mrgentox.2007.10.009
- Trapphoff T, Heiligentag M, El Hajj N, et al. Chronic exposure to a low concentration of bisphenol A during follicle culture affects the epigenetic status of germinal vesicles and metaphase II oocytes. Fertility and Sterility. 2013;100(6): 1758–1767. https://doi.org/10.1016/j.fertnstert.2013.08.021
- Wang T, Han J, Duan X, et al. The toxic effects and possible mechanisms of Bisphenol A on oocyte maturation of porcine in vitro. Oncotarget. 2016;7(22):32554 – 32565. https://doi.org/10.18632/oncotarget.8689
- Eichenlaub-Ritter U, Vogt E, Cukurcam S, at al. Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy. Genetic Toxicology and Environmental Mutagenesis. 2008;651(1-2):82–92. https://doi.org/10.1016/j.mrgentox.2007.10.014
- Can A, Semiz O, Cinar O. Bisphenol A induces cell cycle delay and alters centrosome and spindle microtubular organization in oocytes during meiosis. MHR: Basic Science of Reproductive Medicine. 2005;11(6):389–396. https://doi.org/10.1093/molehr/gah179
- Hunt PA, Koehler KE, Susiarjo M, et al. Bisphenol A exposure causes meiotic aneuploidy in the female mouse. Current Biology. 2003;13:546–553. https://doi.org/10.1016/s0960-9822(03)00189-1
- Hunt PA, Hassold TJ. Human female meiosis: what makes a good egg go bad? Trends in Genetics. 2008;24(2):86–93. https://doi.org/10.1016/j.tig.2007.11.010
- Lenie S, Cortvrindt R, Eichenlaub-Ritter U, Smitz J.. Continuous exposure to bisphenol A during in vitro follicular development induces meiotic abnormalities. Genetic Toxicology and Environmental Mutagenesis. 2008;651(1-2):71–81. https://doi.org/10.1016/j.mrgentox.2007.10.017
- Pan MH, Wu YK, Liao BY, et al. Bisphenol A Exposure Disrupts Organelle Distribution and Functions During Mouse Oocyte Maturation. Frontiers in Cell and Developmental Biology. 2021;9: Article 661155 https://doi.org/10.3389/fcell.2021.661155
- Peretz J, Craig ZR, Flaws JA. Bisphenol A Inhibits Follicle Growth and Induces Atresia in Cultured Mouse Antral Follicles Independently of the Genomic Estrogenic Pathway1. Biology of Reproduction. 2012;87(3):1–11. https://doi.org/10.1095/biolreprod.112.101899
- Chen Y, Zhang S, Sun Y, et al. Bisphenol A impairs oocyte maturation by dysfunction of cumulus cells. Theriogenology. 2024;233:139–146. https://doi.org/10.1016/j.theriogenology.2024.11.023
- Machtinger R, Combelles CMH, Missmer SA, et al. Bisphenol A and human oocyte maturation in vitro. Human Reproduction. 2013;28(10):2735–2745. https://doi.org/10.1093/humrep/det312
- Fujimoto VY, Kim D, vom Saal FS, et al. Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization. Fertility and Sterility. 2011;95(5):1816–1819. https://doi.org/10.1016/j.fertnstert.2010.11.008
- Brukhin GV, Gribachyova NV, Soliannikova DR. To the question of human oocytes dysmorphism and its influence on the parameters of early embryogenesis. Russian Journal of Human Reproduction. 2025;31(3): 48 – 54. https://doi.org/10.17116/repro20253103148
- Faramarzi A, Khalili MA, Omidi M. Morphometric analysis of human oocytes using time lapse: does it predict embryo developmental outcomes? Human Fertility (Cambridge, England). 2019; 22(3): 171–176. https://doi.org/10.1080/14647273.2017.1406670
- Habibzadeh F. Statistical data editing in scientific articles. Journal of Korean Medical Science. 2017;32(7):1072–1076. https//doi.org/10.3346/jkms.2017.32.7.1072
- Misra DP, Zimba O, Gasparyan AY. Statistical data presentation: a primer for rheumatology researchers. Rheumatology International. 2021;41(1):43–55. https//doi.org/10.1007/s00296-020-04740-z
- Dergacheva NI, Patkin EL, Suchkova IO, et al. Bisphenol a and human diseases. Mechanisms of action. Ecological genetics. 2019;17(3):87 – 98. https://doi.org/10.17816/ecogen17387-98
- Besaratinia A. The state of research and weight of evidence on the epigenetic effects of bisphenol A. International Journal of Molecular Sciences. 2023;24:7951. https://doi.org/10.3390/ijms24097951
- Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Human Reproduction Update. 2015;22(2):182–193. https://doi.org/10.1093/humupd/dmv055
- Soriano S, Ripoll C, Alonso-Magdalena P, et al. Effects of bisphenol A on ion channels: experimental evidence and molecular mechanisms. Steroids. 2016;111:12 – 20. https://doi.org/10.1016/j.steroids.2016.02.020
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