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The effect of progesterone administration on the expression of metastasis tumor antigens (MTA1 and MTA3) in placentas of normal and dexamethasone-treated rats

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Abstract

Background

Dexamethasone (DEX) induces intrauterine growth restriction (IUGR) in pregnant rats. IUGR can occur due to apoptosis of trophoblasts, which is believed to be inhibited by progesterone (P4). A group of genes called MTAs play a role in proliferation and apoptosis. MTA1 upregulates trophoblasts proliferation and differentiation, while MTA3 downregulates proliferation and induces apoptosis. Hence, we hypothesized that during IUGR, placental MTA1 decreases and MTA3 increases and this is reversed by P4 treatment.

Methods

Pregnant Sprague–Dawley rats were divided into 4 groups based on daily intraperitoneal injections: control (C, saline), DEX (DEX, 0.2 mg/kg/day), DEX and P4 (DEX + P4, DEX: 0.2 mg/kg/day, P4: 5 mg/kg/day) and P4-treated (P4, 5 mg/kg/day) groups. Injections were started on 15 dg until the day of dissection (19 or 21 dg). Gene and protein expressions of MTA1 and MTA3 were studied in the labyrinth (LZ) and basal (BZ) zones using real-time PCR and Western blotting, respectively.

Results

DEX treatment induced 18% reduction in fetal body weight (p < 0.001) and 30% reduction in placental weight (p < 0.01). Maternal P4 level was also significantly lower in DEX treated groups (p < 0.05). MTA1 expression was decreased in the LZ (gene, p < 0.001) and BZ (protein p < 0.01), while MTA3 protein expression was upregulated in the LZ with DEX treatment (p < 0.001). These changes were reversed with P4 treatment.

Conclusion

The findings of the present study indicate that DEX induces IUGR through changing the expression of placental MTA1 and MTA3 antigens and P4 improved pregnancy outcome by preventing the changes in MTAs expression.

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Acknowledgement

We would like to acknowledge the Research Sector, Kuwait University (Grant No. MY01/17) for funding this project.

Funding

This study was funded by the Research Sector, Kuwait University (Grant No. MY01/17).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Kuwait University, Safat, P.O. Box 13060, Kuwait City, Kuwait

    M. M. Alawadhi, F. Al Shammari, F. Mulla Ali, R. Almatar, A. Al-Duwaikhi & M. D. Al-Bader

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  1. M. M. Alawadhi
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  2. F. Al Shammari
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Correspondence to M. D. Al-Bader.

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Author Prof. Maie D. Al-Bader declares that she has no conflict of interest. Author Dr. Mariam M. Alawadhi declares that she has no conflict of interest. Author Dr. Farah R M Al Shammari declares that she has no conflict of interest. Author Dr. Fatemah H R Mulla Ali declares that she has no conflict of interest. Author Dr. Rama Jamal Almatar declares that she has no conflict of interest. Author Dr. Ayat Hassan Al-Duwaikhi declares that she has no conflict of interest.

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Alawadhi, M.M., Al Shammari, F., Ali, F.M. et al. The effect of progesterone administration on the expression of metastasis tumor antigens (MTA1 and MTA3) in placentas of normal and dexamethasone-treated rats. Mol Biol Rep 49, 1935–1943 (2022). https://doi.org/10.1007/s11033-021-07005-5

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