Startseite Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress

  • Yuko Arita , Hyeon Jeong Park , Aisling Cantillon , Darios Getahun , Ramkumar Menon und Morgan R. Peltier EMAIL logo
Veröffentlicht/Copyright: 24. Juli 2019
Journal of Perinatal Medicine
Aus der Zeitschrift Journal of Perinatal Medicine Band 47 Heft 7

Abstract

Background

Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta.

Methods

Placental explant cultures were treated with BPA (0–10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA).

Results

Under basal conditions, IL-1β and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000–10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1β, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production.

Conclusion

BPA may increase placental inflammation by promoting IL-1β and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.

Keywords: bisphenol-A; cytokines; environmental toxins; neurodevelopment
Corresponding author: Dr. Morgan R. Peltier, Department of Foundations of Medicine, NYU-Long Island School of Medicine, Mineola, NY, USA; Department of Obstetrics and Gynecology; NYU-Long Island School of Medicine, Mineola, NY, USA; and Department of Obstetric and Gynecology, NYU-Winthrop Hospital, 101 Mineola Blvd Rm. 4-040, Mineola, NY, USA, Tel.: +516-663-9796

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Schecter A, Malik N, Haffner D, Smith S, Harris TR, Paepke O, et al. Bisphenol A (BPA) in U.S. food. Environ Sci Technol 2010;44: 9425–30.10.1021/es102785dSuche in Google Scholar PubMed

2. Troisi J, Mikelson C, Richards S, Symes S, Adair D, Zullo F, et al. Placental concentrations of bisphenol A and birth weight from births in the Southeastern U.S. Placenta 2014;35:947–52.10.1016/j.placenta.2014.08.091Suche in Google Scholar PubMed

3. Schonfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect 2002;110:A703–7.10.1289/ehp.021100703Suche in Google Scholar

4. Cao XL, Zhang J, Goodyer CG, Hayward S, Cooke GM, Curran IH. Bisphenol A in human placental and fetal liver tissues collected from Greater Montreal area (Quebec) during 1998–2008. Chemosphere 2012;89:505–11.10.1016/j.chemosphere.2012.05.003Suche in Google Scholar PubMed

5. Zhang J, Cooke GM, Curran IH, Goodyer CG, Cao XL. GC-MS analysis of bisphenol A in human placental and fetal liver samples. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:209–14.10.1016/j.jchromb.2010.11.031Suche in Google Scholar PubMed

6. Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod 2002;17:2839–41.10.1093/humrep/17.11.2839Suche in Google Scholar PubMed

7. Cantonwine D, Meeker JD, Hu H, Sanchez BN, Lamadrid-Figueroa H, Mercado-Garcia A, et al. Bisphenol a exposure in Mexico City and risk of prematurity: a pilot nested case control study. Environ Health 2010;9:62.10.1186/1476-069X-9-62Suche in Google Scholar PubMed PubMed Central

8. Behnia F, Peltier M, Getahun D, Watson C, Saade G, Menon R. High bisphenol A (BPA) concentration in the maternal, but not fetal, compartment increases the risk of spontaneous preterm delivery. J Matern Fetal Neonatal Med 2016;29:3583–9.10.3109/14767058.2016.1139570Suche in Google Scholar PubMed

9. Chou WC, Chen JL, Lin CF, Chen YC, Shih FC, Chuang CY. Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan. Environ Health 2011;10:94.10.1186/1476-069X-10-94Suche in Google Scholar PubMed PubMed Central

10. Leclerc F, Dubois MF, Aris A. Maternal, placental and fetal exposure to bisphenol A in women with and without preeclampsia. Hypertens Pregnancy 2014;33:341–8.10.3109/10641955.2014.892607Suche in Google Scholar PubMed

11. de Cock M, Maas YG, van de Bor M. Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review. Acta Paediatr 2012;101:811–8.10.1111/j.1651-2227.2012.02693.xSuche in Google Scholar PubMed

12. Arita Y, Yeh C, Thoma T, Getahun D, Menon R, Peltier MR. Effect of polybrominated diphenyl ether congeners on placental cytokine production. J Reprod Immunol 2018;125:72–9.10.1016/j.jri.2017.12.002Suche in Google Scholar PubMed

13. Behnia F, Peltier MR, Saade GR, Menon R. Environmental pollutant polybrominated diphenyl ether, a flame retardant, induces primary amnion cell senescence. Am J Reprod Immunol 2015;74:398–406.10.1111/aji.12414Suche in Google Scholar PubMed

14. Tetz LM, Aronoff DM, Loch-Caruso R. Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells. Reprod Biol Endocrinol 2015;13:56.10.1186/s12958-015-0046-8Suche in Google Scholar PubMed PubMed Central

15. Arita Y, Kirk M, Gupta N, Menon R, Getahun D, Peltier MR. Effects of tributyltin on placental cytokine production. J Perinat Med 2018;46:867–75.10.1515/jpm-2017-0336Suche in Google Scholar PubMed

16. Peltier MR, Arita Y, Klimova NG, Gurzenda EM, Koo HC, Murthy A, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation. J Reprod Immunol 2013;98:10–20.10.1016/j.jri.2013.02.005Suche in Google Scholar PubMed PubMed Central

17. Peltier MR. Immunology of term and preterm labor. Reprod Biol Endocrinol 2003;1:122.10.1186/1477-7827-1-122Suche in Google Scholar PubMed PubMed Central

18. Hsiao EY, Patterson PH. Placental regulation of maternal-fetal interactions and brain development. Dev Neurobiol 2012;72:1317–26.10.1002/dneu.22045Suche in Google Scholar PubMed

19. Alizadeh M, Ota F, Hosoi K, Kato M, Sakai T, Satter MA. Altered allergic cytokine and antibody response in mice treated with Bisphenol A. J Med Invest 2006;53:70–80.10.2152/jmi.53.70Suche in Google Scholar PubMed

20. Youn JY, Park HY, Lee JW, Jung IO, Choi KH, Kim K, et al. Evaluation of the immune response following exposure of mice to bisphenol A: induction of Th1 cytokine and prolactin by BPA exposure in the mouse spleen cells. Arch Pharm Res 2002;25:946–53.10.1007/BF02977018Suche in Google Scholar PubMed

21. Watanabe H, Adachi R, Kusui K, Hirayama A, Kasahara T, Suzuki K. Bisphenol A significantly enhances the neutrophilic differentiation of promyelocytic HL-60 cells. Int Immunopharmacol 2003;3:1601–8.10.1016/S1567-5769(03)00182-6Suche in Google Scholar PubMed

22. Lee MH, Chung SW, Kang BY, Park J, Lee CH, Hwang SY, et al. Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+. Immunology 2003;109:76–86.10.1046/j.1365-2567.2003.01631.xSuche in Google Scholar PubMed PubMed Central

23. Sugita-Konishi Y, Shimura S, Nishikawa T, Sunaga F, Naito H, Suzuki Y. Effect of Bisphenol A on non-specific immunodefenses against non-pathogenic Escherichia coli. Toxicol Lett 2003;136:217–27.10.1016/S0378-4274(02)00388-0Suche in Google Scholar PubMed

24. Savastano S, Tarantino G, D’Esposito V, Passaretti F, Cabaro S, Liotti A, et al. Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance: a cross-sectional study on adult male population. J Transl Med. 2015;13:169.10.1186/s12967-015-0532-ySuche in Google Scholar PubMed PubMed Central

25. Stein TP, Schluter MD, Steer RA, Guo L, Ming X. Bisphenol A exposure in children with autism spectrum disorders. Autism Res 2015;8:272–83.10.1002/aur.1444Suche in Google Scholar PubMed PubMed Central

26. Couleau N, Falla J, Beillerot A, Battaglia E, D’Innocenzo M, Plancon S, et al. Effects of endocrine disruptor compounds, alone or in combination, on human macrophage-like THP-1 cell Response. PLoS One 2015;10:e0131428.10.1371/journal.pone.0131428Suche in Google Scholar PubMed PubMed Central

27. Liu Y, Mei C, Liu H, Wang H, Zeng G, Lin J, et al. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A. Biochem Biophys Res Commun 2014;451:592–8.10.1016/j.bbrc.2014.08.031Suche in Google Scholar PubMed

28. Ben-Jonathan N, Hugo ER, Brandebourg TD. Effects of bisphenol A on adipokine release from human adipose tissue: implications for the metabolic syndrome. Mol Cell Endocrinol 2009;304:49–54.10.1016/j.mce.2009.02.022Suche in Google Scholar PubMed PubMed Central

29. Zhu J, Jiang L, Liu Y, Qian W, Liu J, Zhou J, et al. MAPK and NF-kappaB pathways are involved in bisphenol A-induced TNF-alpha and IL-6 production in BV2 microglial cells. Inflammation 2015;38:637–48.10.1007/s10753-014-9971-5Suche in Google Scholar PubMed

30. Romero R, Sepulveda W, Kenney JS, Archer LE, Allison AC, Sehgal PB. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp 1992;167:205–20; discussion 20–3.10.1002/9780470514269.ch13Suche in Google Scholar PubMed

31. Yoshimura K, Hirsch E. Interleukin-6 is neither necessary nor sufficient for preterm labor in a murine infection model. J Soc Gynecol Investig 2003;10:423–7.10.1016/S1071-55760300138-2Suche in Google Scholar

32. Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 2007;27:10695–702.10.1523/JNEUROSCI.2178-07.2007Suche in Google Scholar PubMed PubMed Central

33. Jang YJ, Park HR, Kim TH, Yang WJ, Lee JJ, Choi SY, et al. High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations. Toxicology 2012;296:73–82.10.1016/j.tox.2012.03.007Suche in Google Scholar PubMed

34. Acconcia F, Pallottini V, Marino M. Molecular mechanisms of action of BPA. Dose Response 2015;13:1559325815610582.10.1177/1559325815610582Suche in Google Scholar PubMed PubMed Central

35. Hiroi H, Tsutsumi O, Momoeda M, Takai Y, Osuga Y, Taketani Y. Differential interactions of bisphenol A and 17beta-estradiol with estrogen receptor alpha (ERalpha) and ERbeta. Endocr J 1999;46:773–8.10.1507/endocrj.46.773Suche in Google Scholar PubMed

36. Sui Y, Ai N, Park SH, Rios-Pilier J, Perkins JT, Welsh WJ, et al. Bisphenol A and its analogues activate human pregnane X receptor. Environ Health Perspect 2012;120:399–405.10.1289/ehp.1104426Suche in Google Scholar PubMed PubMed Central

37. Ferguson KK, Cantonwine DE, McElrath TF, Mukherjee B, Meeker JD. Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative stress in pregnancy. Reprod Toxicol 2016;66:93–8.10.1016/j.reprotox.2016.10.002Suche in Google Scholar PubMed PubMed Central

38. Watkins DJ, Ferguson KK, Anzalota Del Toro LV, Alshawabkeh AN, Cordero JF, Meeker JD. Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico. Int J Hyg Environ Health 2015;218:212–9.10.1016/j.ijheh.2014.11.001Suche in Google Scholar PubMed PubMed Central

39. Hong CC, Shimomura-Shimizu M, Muroi M, Tanamoto K. Effect of endocrine disrupting chemicals on lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by mouse macrophages. Biol Pharm Bull 2004;27:1136–9.10.1248/bpb.27.1136Suche in Google Scholar PubMed

40. Teixeira D, Marques C, Pestana D, Faria A, Norberto S, Calhau C, et al. Effects of xenoestrogens in human M1 and M2 macrophage migration, cytokine release, and estrogen-related signaling pathways. Environ Toxicol 2016;31:1496–509.10.1002/tox.22154Suche in Google Scholar PubMed

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2019-0045).

Received: 2019-02-14
Accepted: 2019-06-17
Published Online: 2019-07-24
Published in Print: 2019-09-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Corner of Academy
  3. Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study
  4. Original Articles – Obstetrics
  5. Poor sleep quality is associated with perinatal depression. A systematic review of last decade scientific literature and meta-analysis
  6. The predictive value of serum cancer antigen 125 (CA125) levels on pregnancy outcome in threatened miscarriages
  7. Pregnancy outcomes after thyroid cancer
  8. Maternal and perinatal outcomes in external cephalic version: prognostic factors for the success of the technique
  9. Association of dietary intake below recommendations and micronutrient deficiencies during pregnancy and low birthweight
  10. The sFlt-1/PlGF ratio values within the <38, 38–85 and >85 brackets as compared to perinatal outcomes
  11. Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress
  12. Standard and adjusted criteria for the use of the misoprostol vaginal insert for labor induction: a comparative cohort study
  13. New reference values for biometrical measurements and sonographic estimated fetal weight in twin gestations and comparison to previous normograms
  14. Simultaneous analysis of bisphenol A fractions in maternal and fetal compartments in early second trimester of pregnancy
  15. Original Articles – Fetus
  16. Antenatal ultrasound compared to MRI evaluation of fetal myelomeningocele: a prenatal and postnatal evaluation
  17. The value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) parameters in analysis with fetal malnutrition neonates
  18. Carboxyhemoglobin in umbilical cord blood and maternal smoking
  19. Original Article – Newborn
  20. Macronutrient analysis of preterm human milk using mid-infrared spectrophotometry
https://doi.org/10.1515/jpm-2019-0045
Schlagwörter für diesen Artikel
bisphenol-A; cytokines; environmental toxins; neurodevelopment

Artikel in diesem Heft

  1. Frontmatter
  2. Corner of Academy
  3. Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study
  4. Original Articles – Obstetrics
  5. Poor sleep quality is associated with perinatal depression. A systematic review of last decade scientific literature and meta-analysis
  6. The predictive value of serum cancer antigen 125 (CA125) levels on pregnancy outcome in threatened miscarriages
  7. Pregnancy outcomes after thyroid cancer
  8. Maternal and perinatal outcomes in external cephalic version: prognostic factors for the success of the technique
  9. Association of dietary intake below recommendations and micronutrient deficiencies during pregnancy and low birthweight
  10. The sFlt-1/PlGF ratio values within the <38, 38–85 and >85 brackets as compared to perinatal outcomes
  11. Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress
  12. Standard and adjusted criteria for the use of the misoprostol vaginal insert for labor induction: a comparative cohort study
  13. New reference values for biometrical measurements and sonographic estimated fetal weight in twin gestations and comparison to previous normograms
  14. Simultaneous analysis of bisphenol A fractions in maternal and fetal compartments in early second trimester of pregnancy
  15. Original Articles – Fetus
  16. Antenatal ultrasound compared to MRI evaluation of fetal myelomeningocele: a prenatal and postnatal evaluation
  17. The value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) parameters in analysis with fetal malnutrition neonates
  18. Carboxyhemoglobin in umbilical cord blood and maternal smoking
  19. Original Article – Newborn
  20. Macronutrient analysis of preterm human milk using mid-infrared spectrophotometry
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 27.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jpm-2019-0045/html
Button zum nach oben scrollen