Skip to main content

Advertisement

Log in

Effects of bone marrow-derived mesenchymal stem cells exposed to endocrine-disrupting chemicals on the differentiation of umbilical cord blood hematopoietic stem cells

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Endocrine-disrupting chemicals (EDCs), a class of peripheral toxic substances, can cause many environmental and clinical side effects, particularly on the human body’s endocrine system. Bisphenol A (BPA) and diethylhexyl phthalate (DEHP) are two well-known EDCs in the medicine industry. However, there are no comprehensive studies on their effects on hematopoiesis. Hence, this study aimed to investigate the effect of these two aforementioned substances on the clonogenic capacity of umbilical cord blood hematopoietic stem cells (CB-HSCs). The HSCs which express CD34 + were isolated from umbilical cord blood by the magnetic-activated cell sorting (MACS) system. To investigate the effects of different optimized concentrations of BPA and DEHP, CB-CD34+ HSCs were exposed to EDCs in semisolid medium. For evaluation of coexposures, CB-CD34+ HSCs were cocultured with bone marrow-derived mesenchymal stem cells (BM-MSCs) in the presence of BPA and DEHP. Finally, the number and types of colonies were evaluated after 14 days. Statistical analysis was performed by GraphPad Prism through ANOVA. CB-HSC treated by BPA and DEHP showed a lower absolute colony count than the control group (P < 0.05). Decrease in clonogenic potential of HSCs was more significant in coculture condition by MSCs. In particular, there was a significant decrease in the BFU-E colonies in comedicated-derived fractions (P < 0.0001). In the presence of EDCs such as BPA and DEHP, the patterns of differentiation in CD34+ CB-HSCs changed from suppressed erythroid differentiation toward stimulated myelogenesis pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Availability of data and material

Please contact corresponding author (S.A.) for data requests.

Code availability

Not applicable.

Abbreviations

BFU-E:

Burst-forming unit-erythroid

BPA:

Bisphenol A

BM-MSC:

Bone marrow-derived mesenchymal stem cells

CFU-E:

Colony-forming unit-erythroid

CFU-GM:

Colony-forming unit-granulocyte-monocyte

CFU-GEMM:

Colony-forming unit-granulocyte erythrocyte-monocyte-megakaryocyte

CFU-G:

Colony-forming unit-granulocyte

CFU-M:

Colony-forming unit-monocyte

CPDA1:

Citrate-phosphate-dextrose adenine

CB-HSC:

Cord blood hematopoietic stem cell

DEHP:

Diethylhexyl phthalate

DDT:

Dichlorodiphenyltrichloroethane

EDC:

Endocrine-disrupting chemical

FBS:

Fetal bovine serum

G-CSF:

Granulocyte colony-stimulating factor

MNC:

Mononuclear cell

PCBs:

Polychlorinated biphenyls

PBBs:

Polybrominated biphenyls

PVC:

Polyvinyl chloride

SCF:

Stem cell factor

TPO:

Thrombopoietin

UCB:

Umbilical cord blood

References

  • Abnosi MH, Aliyari Babolghani Z (2020) The inhibitory role of Di-2-ethylhexyl phthalate on osteogenic differentiation of mesenchymal stem cells via down-regulation of RUNX2 and membrane function impairment. International Journal of Medical Toxicology and Forensic Medicine 10(2):26673

    Article  Google Scholar 

  • Agas D, Lacava G, Sabbieti MG (2019) Bone and bone marrow disruption by endocrine-active substances. J Cell Physiol 234(1):192–213

    Article  CAS  Google Scholar 

  • Agas D, Sabbieti MG, Marchetti L (2013) Endocrine disruptors and bone metabolism. Arch Toxicol 87(4):735–751

    Article  CAS  Google Scholar 

  • Ahmadi Z, Moradabadi A, Abdollahdokht D, Mehrabani M, Nematollahi MH (2019) Association of environmental exposure with hematological and oxidative stress alteration in gasoline station attendants. Environ Sci Pollut Res Int 26(20):20411–20417

    Article  CAS  Google Scholar 

  • Ambrosi TH, Scialdone A, Graja A, Gohlke S, Jank AM, Bocian C, Woelk L, Fan H, Logan DW, Schurmann A, Saraiva LR, Schulz TJ (2017) Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20(6):771-784.e776

    Article  CAS  Google Scholar 

  • AuBuchon JP, Estep TN, Davey RJ (1988) The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs. Blood 71(2):448–452

    Article  CAS  Google Scholar 

  • Bateman ME, Strong AL, McLachlan JA, Burow ME, Bunnell BA (2016) The effects of endocrine disruptors on adipogenesis and osteogenesis in mesenchymal stem cells: a review. Front Endocrinol (lausanne) 7:171

    Google Scholar 

  • Birnbaum LS (2013) State of the science of endocrine disruptors. Environ Health Perspect 121(4):A107

    Google Scholar 

  • Boas M, Feldt-Rasmussen U, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355(2):240–248

    Article  CAS  Google Scholar 

  • Bontempo P, Mita L, Doto A, Miceli M, Nebbioso A, Lepore I, Franci G, Menafra R, Carafa V, Conte M, De Bellis F, Manzo F, Di Cerbo V, Benedetti R, D’Amato L, Marino M, Bolli A, Del Pozzo G, Diano N, Portaccio M, Mita GD, Vietri MT, Cioffi M, Nola E, Dell’aversana C, Sica V, Molinari AM, Altucci L (2009) Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells. J Transl Med 7:48–48

    Article  Google Scholar 

  • Cano R, Pérez JL, Dávila LA, Ortega Á, Gómez Y, Valero-Cedeño NJ, Parra H, Manzano A, Véliz Castro TI, Albornoz MPD (2021) Role of Endocrine-disrupting chemicals in the pathogenesis of non-alcoholic fatty liver disease: a comprehensive review. Int J Mol Sci 22(9):4807

    Article  CAS  Google Scholar 

  • Chang-Yi, T., F. Te-Ping, C. Shuoh-Wen, C. Hsiao-Wen, L. Eric Chang-Yi, L. Ting-An, T. Der-Cherng and I. C. Yuan (2021). Research Square.

  • Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30(4):293–342

    Article  CAS  Google Scholar 

  • Doull J, Cattley R, Elcombe C, Lake BG, Swenberg J, Wilkinson C, Williams G, van Gemert M (1999) A cancer risk assessment of di(2-ethylhexyl)phthalate: application of the new U.S. EPA Risk Assessment Guidelines. Regul Toxicol Pharmacol 29(3):327–357

    Article  CAS  Google Scholar 

  • Gore, A., D. Crews, L. Doan, M. Merrill, H. Patisaul and A. Zota (2014). Introduction to endocrine disrupting chemicals (EDCs)—a guide for public interest organizations and policy makers. Endocrine Society reports and white papers.

  • Gutiérrez-García AK, Flores-Kelly JM, Ortiz-Rodríguez T, Kalixto-Sánchez MA, De León-Rodríguez A (2019) Phthalates affect the in vitro expansion of human hematopoietic stem cell. Cytotechnology 71(2):553–561

    Article  Google Scholar 

  • Haq MEU, Akash MSH, Sabir S, Mahmood MH, Rehman K (2020) Human exposure to bisphenol A through dietary sources and development of diabetes mellitus: a cross-sectional study in Pakistani population. Environ Sci Pollut Res 27(21):26262–26275

    Article  CAS  Google Scholar 

  • Hu W-Y, Shi G-B, Hu D-P, Nelles JL, Prins GS (2012) Actions of estrogens and endocrine disrupting chemicals on human prostate stem/progenitor cells and prostate cancer risk. Mol Cell Endocrinol 354(1–2):63–73

    Article  CAS  Google Scholar 

  • Kahn LG, Philippat C, Nakayama SF, Slama R, Trasande L (2020) Endocrine-disrupting chemicals: implications for human health. Lancet Diabetes Endocrinol 8(8):703–718

    Article  CAS  Google Scholar 

  • Kajta M, Wójtowicz AK (2013) Impact of endocrine-disrupting chemicals on neural development and the onset of neurological disorders. Pharmacol Rep 65(6):1632–1639

    Article  CAS  Google Scholar 

  • Kopras E, Potluri V, Bermudez ML, Williams K, Belcher S, Kasper S (2014) Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease. Endocr Relat Cancer 21(2):T1-12

    Article  CAS  Google Scholar 

  • Kumar M, Sarma DK, Shubham S, Kumawat M, Verma V, Prakash A, Tiwari R (2020) Environmental endocrine-disrupting chemical exposure: role in non-communicable diseases. Front Public Health 8:553850

    Article  Google Scholar 

  • La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, Guyton KZ, Kortenkamp A, Cogliano VJ, Woodruff TJ (2020) Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol 16(1):45–57

    Article  Google Scholar 

  • Latini G (2005) Monitoring phthalate exposure in humans. Clin Chim Acta 361(1):20–29

    Article  CAS  Google Scholar 

  • Lu J, Wu J, Stoffella PJ, Wilson PC (2015) Uptake and distribution of bisphenol A and nonylphenol in vegetable crops irrigated with reclaimed water. J Hazard Mater 283:865–870

    Article  CAS  Google Scholar 

  • Manz P, Cadeddu RP, Wilk M, Fischer JC, Fritz B, Haas R, Wenzel F (2015) Influence of Di(2-ethylhexyl)phthalate on migration rate and differentiation of human hematopoietic stem and progenitor cells (CD34+). Clin Hemorheol Microcirc 61(2):111–118

    Article  CAS  Google Scholar 

  • Michalowicz J, Mokra K, Bak A (2015) Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study). Toxicol in Vitro 29(7):1464–1472

    Article  CAS  Google Scholar 

  • Mousavi Z, Yazdani Z, Moradabadi A, Hoseinpourkasgari F, Hassanshahi G (2019) Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review. Exp Hematol Oncol 8(1):1–6

    Article  CAS  Google Scholar 

  • Nowak K, Jabłońska E, Ratajczak-Wrona W (2019) Immunomodulatory effects of synthetic endocrine disrupting chemicals on the development and functions of human immune cells. Environ Int 125:350–364

    Article  CAS  Google Scholar 

  • Sampson J, de Korte D (2011) DEHP-plasticised PVC: relevance to blood services. Transfus Med 21(2):73–83

    Article  CAS  Google Scholar 

  • Shariati A, Moradabadi A, Azimi T, Ghaznavi-Rad E (2020) Wound healing properties and antimicrobial activity of platelet-derived biomaterials. Sci Rep 10(1):1–9

    Article  Google Scholar 

  • Shaz BH, Grima K, Hillyer CD (2011) 2-(Diethylhexyl) phthalate in blood bags: is this a public health issue? Transfusion 51(11):2510–2517

    Article  CAS  Google Scholar 

  • Street ME, Angelini S, Bernasconi S, Burgio E, Cassio A, Catellani C, Cirillo F, Deodati A, Fabbrizi E, Fanos V (2018) Current knowledge on endocrine disrupting chemicals (EDCs) from animal biology to humans, from pregnancy to adulthood: highlights from a national Italian meeting. Int J Mol Sci 19(6):1647

    Article  Google Scholar 

  • Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK, McLachlan JA, Nephew KP, Burow ME, Bunnell BA (2015) Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human mesenchymal stem cells. Environ Health Perspect 123(1):42–48

    Article  Google Scholar 

  • Toni R, Di Conza G, Barbaro F, Zini N, Consolini E, Dallatana D, Antoniel M, Quarantini E, Quarantini M, Maioli S, Bruni CA, Elviri L, Panseri S, Sprio S, Sandri M, Tampieri A (2020) Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors. Front Immunol 11:1737

    Article  CAS  Google Scholar 

  • Tsoi WC (2016) Advances in blood storage bags and preservative solutions. ISBT Sci Ser 11(S2):49–54

    Article  Google Scholar 

  • Vom Saal FS, Nagel SC, Coe BL, Angle BM, Taylor JA (2012) The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Mol Cell Endocrinol 354(1–2):74–84

    Article  Google Scholar 

  • Worley JR, Parker GC (2019) Effects of environmental stressors on stem cells. World Journal of Stem Cells 11(9):565

    Article  Google Scholar 

  • Xin, F., L. M. Smith, M. Susiarjo, M. S. Bartolomei and K. J. Jepsen (2018). "Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system." Environmental epigenetics 4(2): dvy002.

  • Yang O, Kim HL, Weon J-I, Seo YR (2015) Endocrine-disrupting chemicals: review of toxicological mechanisms using molecular pathway analysis. Journal of Cancer Prevention 20(1):12

    Article  Google Scholar 

  • Yazdani Z, Mousavi Z, Moradabadi A, Hassanshahi G (2020) Significance of CXCL12/CXCR4 Ligand/receptor axis in various aspects of acute myeloid leukemia. Cancer Management and Research 12:2155

    Article  CAS  Google Scholar 

  • Yilmaz B, Terekeci H, Sandal S, Kelestimur F (2020) Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Rev Endocr Metab Disord 21(1):127–147

    Article  CAS  Google Scholar 

  • Zarean M, Keikha M, Poursafa P, Khalighinejad P, Amin M, Kelishadi R (2016) A systematic review on the adverse health effects of di-2-ethylhexyl phthalate. Environ Sci Pollut Res 23(24):24642–24693

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All of the authors and coauthors who were listed on the title page greatly helped to accomplish this study with unsparing efforts. A.S. helped prepare the last version of the manuscript and perform a literature review. She also mainly contributed to conducting the experiment, data curation, data analysis, designation of images and tables, final arrangement of the data-making structure of the study, and visualization. S.A. mainly performed project supervision/correspondence, project administration, conceptualization, scientific consultations, and verification of the manuscript by definitive approval for submission. He also academically and grammatically performed peer revision and major conceptualization qualifying. F.A. equally helped A.S. for conducting experiment. MA.G equally helped A.S. for biostatistical analysis of data. S.A. and A.S. equally helped with critical revision of the manuscript on the important intellectual content according to the journal’s instructions, validation of data, and designation of methodological strategies. All of the authors and coauthors attest to the fact that they have approved the final version of the article, and they have received an electronic copy of the manuscript. Additionally, they attest to the validity and legitimacy of the data and agreed to submit this manuscript to this journal.

Corresponding author

Correspondence to Saeid Abroun.

Ethics declarations

Ethical considerations

This experimental study accessed ethics approval from the Research Ethics Committee of Tarbiat Modares University (Tehran, Iran). The study was performed in accordance standard of Declaration of Helsinki.

Consent to participate

All healthy BM-MSC donors provided written informed consent and contributed to the study.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible editor: Lotfi Aleya.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soltani, A., Abroun, S., Abbasnejadshani, F. et al. Effects of bone marrow-derived mesenchymal stem cells exposed to endocrine-disrupting chemicals on the differentiation of umbilical cord blood hematopoietic stem cells. Environ Sci Pollut Res 29, 39903–39913 (2022). https://doi.org/10.1007/s11356-021-17787-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-17787-7

Keywords

Navigation