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In vitro–Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model

  • Reproductive Biology: Original Article
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Abstract  

Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro–generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro–generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro–generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro–generated MDSCs could be considered as a potential approach to reduce these complications.

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Data and material will be available if demanded.

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Abbreviations

MDSC:

Myeloid-derived suppressor cell

G-MDSC:

Granulocytic myeloid-derived suppressor cell

M-MDSC:

Monocytic myeloid-derived suppressor cell

RSA:

Recurrent spontaneous abortion

TGF-β:

Transforming growth factor beta

Arg-1:

Arginase-1

IDO:

Indoleamine 2,3-dioxygenase

INOS:

Inducible nitric oxide synthase

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

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Acknowledgements

The authors would like to thank the Comparative Medicine Center of Shiraz University of Medical Sciences for providing appropriate conditions for establishing the mouse model.

Funding

This paper was extracted from the PhD thesis done by Moslem Ahmadi and was financially supported by Shiraz University of Medical Sciences (grant number 16763).

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Authors and Affiliations

  1. Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

    Moslem Ahmadi, Mahsa Sadat Hosseini & Behrouz Gharesi-Fard

  2. Department of Immunology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

    Mohammad Ali-Hassanzadeh

  3. Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Behrouz Gharesi-Fard

Authors
  1. Moslem Ahmadi
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  2. Mohammad Ali-Hassanzadeh
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  3. Mahsa Sadat Hosseini
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  4. Behrouz Gharesi-Fard
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Corresponding author

Correspondence to Behrouz Gharesi-Fard.

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Ethical Approval.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1398.404).

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Ahmadi, M., Ali-Hassanzadeh, M., Hosseini, M.S. et al. In vitro–Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model. Reprod. Sci. 30, 1217–1228 (2023). https://doi.org/10.1007/s43032-022-00995-y

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  • DOI: https://doi.org/10.1007/s43032-022-00995-y

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