Interference of Bisphenol A on Cumulus Cells Development and Number of Retrieved Mature Oocytes in Unexpected Poor Ovarian Response Women: A Prospective Cohort Study

Document Type : Original Article

Authors

1 Department of Biology, Science, and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Breast Disease Research Center (BDRC), Tehran University of Medical Science, Tehran, Iran

4 Department of Obstetrics and Gynecology, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

Abstract

Objective: This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations
with alterations in the expressions of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 genes and the number of
retrieved mature oocytes (MII oocyte) in the cumulus cells of infertile poor ovarian response stimulates women.
Materials and Methods:In this prospective cohort study, 80 infertile unexpected poor ovarian response (POR) subjects
were selected on the basis of subgroup 1a of the POSEIDON classification. They were divided into two groups: group
1 consisted of 40 women, each with a higher number of metaphase II (MII) oocytes (G1, 3-4 oocytes retrieved), while
group 2 comprised of 40 women, each with a lower number of MII oocytes (G2, ≤2 oocytes retrieved). The expressions
of the studied genes were evaluated by quantitative-real time polymerase chain reaction (PCR). The concentration of
BPA in follicular fluid was measured with HPLC.
Results: The expression levels of NOTCH1-3, HLA-G, and ICAM-1 genes were significantly lower in G2 than G1
(P<0.05). Meanwhile, CASPASE 3/7 expression levels were higher in unexpected POR patients in G2 compared to
G1 (P<0.05). There was a significant direct correlation between the levels of NOTCH1-3, HLA-G and ICAM-1 gene
expressions and there was also a significant inverse correlation (P<0.05) between the levels of CASPASE 3/7, with the
number of MII oocytes and embryo development between the two groups. The concentration of BPA in the follicular
fluids of G2 was higher compared to G1 (P<0.05).
Conclusion: A higher concentration of BPA was associated with a lower number of mature oocytes and oocyte quality
in these patients. Also, alterations of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 transcript levels in unexpected
POR women were associated with BPA concentration.

Keywords

Main Subjects


  1. Noli SA, Ferrari S, Ricci E, Reschini M, Cipriani S, Dallagiovanna C, et al. The role of diet in unexpected poor response to ovarian stimulation: a cross-sectional study. Reprod Biomed Online. 2020; 41(5): 874-883.
  2. Borgatti M, Rizzo R, Canto MB, Fumagalli D, Renzini MM, Fadini R, et al. Release of sICAM-1 in oocytes and in vitro fertilized human embryos. PLoS One. 2008; 3(12): e3970.
  3. Baker VL, Gracia C, Glassner MJ, Schnell VL, Doody K, Coddington CC, et al. Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation. Fertil Steril. 2018; 110(3): 506-513. e3.
  4. Zhou W, Fang F, Zhu W, Chen ZJ, Du Y, Zhang J. Bisphenol A and ovarian reserve among infertile women with polycystic ovarian syndrome. Int J Environ Res Public Health. 2016; 14(1): 18.
  5. Santangeli S, Maradonna F, Olivotto I, Piccinetti CC, Gioacchini G, Carnevali O. Effects of BPA on female reproductive function: The involvement of epigenetic mechanism. Gen Comp Endocrinol. 2017; 245: 122-126.
  6. Ding ZM, Jiao XF, Wu D, Zhang JY, Chen F, Wang YS, et al. Bisphenol AF negatively affects oocyte maturation of mouse in vitro through increasing oxidative stress and DNA damage. Chem Biol Interact. 2017; 278: 222-229.
  7. Vanorny DA, Mayo KE. The role of Notch signaling in the mammalian ovary. Reproduction. 2017; 153(6): R187-R204.
  8. Jukic AM, Calafat AM, McConnaughey DR, Longnecker MP, Hoppin JA, Weinberg CR, et al. Urinary concentrations of phthalate metabolites and bisphenol A and associations with follicular-phase length, luteal-phase length, fecundability, and early pregnancy loss. Environ Health Perspect. 2016; 124(3): 321-328.
  9. Akın L, Kendirci M, Narin F, Kurtoglu S, Saraymen R, Kondolot M, et al. The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls. Acta Paediatr. 2015; 104(4): e171-e177.
  10. Liu Y, Pan Z, Wu Y, Song J, Chen J. Comparison of anti-Müllerian hormone and antral follicle count in the prediction of ovarian response: a systematic review and meta-analysis. J Ovarian Res. 2023 Jun 27;16(1):117.
  11. Domingo-Domenech J, Vidal SJ, Rodriguez-Bravo V, Castillo- Martin M, Quinn SA, Rodriguez-Barrueco R, et al. Suppression of acquired docetaxel resistance in prostate cancer through depletion of Notch- and hedgehog-dependent tumor-initiating cells. Cancer Cell. 2012;373-388 :)3(22 .
  12. Borman ED, Foster WG, Greenacre MK, Muir CC, deCatanzaro D. Stress lowers the threshold dose at which bisphenol A disrupts blastocyst implantation, in conjunction with decreased uterine closure and e-cadherin. Chem Biol Interact. 2015; 237: 87-95.
  13. Crawford BR, Decatanzaro D. Disruption of blastocyst implantation by triclosan in mice: impacts of repeated and acute doses and combination with bisphenol-A. Reprod Toxicol. 2012; 34(4): 607-613.
  14. Fiori F, Parpinel M, Morreale F, Pellegrini N. The Update of the italian food composition database of gluten-free products and its application in food-based dietary guidelines menus. Nutrients. 2022; 14(19): 4171.
  15. Jeong HG, Kim SK, Lee JR, Jee BC. Correlation of oocyte number with serum anti-Müllerian hormone levels measured by either Access or Elecsys in fresh in vitro fertilization cycles. Clin Exp Reprod Med. 2022 Sep;49(3):202-209. doi: 10.5653/ cerm.2022.05211. Epub 2022 Aug 31.
  16. Caserta D, Ciardo F, Bordi G, Guerranti C, Fanello E, Perra G, et al. Correlation of endocrine disrupting chemicals serum levels and white blood cells gene expression of nuclear receptors in a population of infertile women. Int J Endocrinol. 2013; 2013: 510703.
  17. Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-Müllerian hormone and antral follicle count as biomarkers of ovarian response. Hum Reprod Update. 2015 Nov-Dec;21(6):698-710.
  18. Salehi E, Aflatoonian R, Moeini A, Yamini N, Asadi E, Khosravizadeh Z, et al. Apoptotic biomarkers in cumulus cells in relationto embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017; 296(6): 1219-1227.
  19. Nishikawa M, Iwano H, Yanagisawa R, Koike N, Inoue H, Yokota H. Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus. Environ Health Perspect. 2010; 118(9): 1196-1203.
  20. Aftabsavad S, Noormohammadi Z, Moini A, Karimipoor M. Effect of bisphenol A on alterations of ICAM-1 and HLA-G genes expression and DNA methylation profiles in cumulus cells of infertile women with poor response to ovarian stimulation. Sci Rep. 2021; 11(1): 9595.
  21. Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S. Interventions for ‘poor responders’ to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010; (1): CD004379.
  22. Bahrami N, Nazari A, Afshari Z, Aftabsavad S, Moini A, Noormohammadi Z. Gene expression and demographic analyses in women with the poor ovarian response: a computational approach. J Assist Reprod Genet. 2023; 40(11): 2627-2638.
  23. Polyzos NP, Devroey P. A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? Fertil Steril. 2011; 96(5): 1058-1061. e7.
  24. Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013; 42: 132-155.
  25. Ricci E, Noli S, Cipriani S, La Vecchia I, Chiaffarino F, Ferrari S, et al. Maternal and paternal caffeine intake and ART outcomes in couples referring to an italian fertility clinic: a prospective cohort. Nutrients. 2018; 10(8): 1116.
  26. Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, Caspase-3 and Caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013; 14: 32.
  27. Eskew AM, Bedrick BS, Chavarro JE, Riley JK, Jungheim ES. Dietary patterns are associated with improved ovarian reserve in overweight and obese women: a cross-sectional study of the Lifestyle and Ovarian Reserve (LORe) cohort. Reprod Biol Endocrinol. 2022 Feb 19;20(1):33
  28. Farimani M, Nazari A, Mohammadi S, Anvari Aliabad R. Evaluation of intra-ovarian platelet-rich plasma administration on oocytes-dependent variables in patients with poor ovarian response: A retrospective study according to the POSEIDON criteria. Reprod Biol Endocrinol. 2021 Sep 8;19(1):137.
  29. Huo X, Chen D, He Y, Zhu W, Zhou W, Zhang J. Bisphenol-A and female infertility: a possible role of gene-environment interactions. Int J Environ Res Public Health. 2015; 12(9): 11101- 11116.
  30. Miao M, Yuan W, Zhu G, He X, Li DK. In utero exposure to bisphenol- A and its effect on birth weight of offspring. Reprod Toxicol. 2011; 32(1): 64-68.
  31. Li Y, Liu S, Gao F, Peng Z, Zhang J, Li S, et al. BPA interferes with granulosa cell development and oocyte meiosis in mouse preantral follicles. Exp Biol Med (Maywood). 2023; 248(13): 1145-1158.
  32. Nagels HE, Rishworth JR, Siristatidis CS, Kroon B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2015; 2015(11): CD009749.