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Modulation of IL10 and Its Receptor Subunits in Normal and Progesterone-Prolonged Gestation in the Mouse

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Abstract

These experiments aimed to understand the relationship between interleukin 10 (IL10), the IL10 receptor subunits, and progesterone (P4) at the time of parturition. We hypothesized that there is a biologic connection between IL10 and P4, supporting an immunomodulatory mechanism for the onset of labor. Using samples from control and P4-treated pregnant mice, we assessed the production of IL10 and its receptor subunits (IL10Rα and IL10Rβ) in gestational tissues. After preliminary studies, P4-treated pregnant mice were compared with controls to assess for differences in IL10 and IL10 receptor subunit expression throughout gestation. To investigate the contribution of the P4 receptor at the onset of labor, we performed timed studies on pregnant mice after treatment with RU486. Samples collected included placentas, placentation sites, and maternal livers. IL10, IL10Rα, and IL10Rβ levels were measured in homogenized tissue using ELISA assays; the cytokine results were normalized for homogenate protein concentration. Control mice delivered on gd 18–19, and P4 treatment prevented parturition to beyond gd 20, as expected. In treated mice, P4 not only prevented the anticipated nadir of IL10 at term, but maintained elevated levels of IL10 through gd 20 (p < 0.05). P4 also reversed the anticipated decrease of the IL10Rα, which was increased in P4-treated mice (p < 0.05). Treatment with RU486 did not modulate the expression of IL10 or IL10Rα, but showed a significant decrease in the level of IL10Rβ (p < 0.05). Progesterone functions at least in part through the IL10 signaling pathway to prolong gestation.

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Funding

This work was funded by the Burroughs-Welcome Fund Preterm Birth Initiative.

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Authors and Affiliations

  1. Division of Maternal-Fetal Medicine and the Vincent Center for Reproductive Biology, Department of Obstetrics & Gynecology, Massachusetts General Hospital, Boston, MA, USA

    Ingrid Liff, Sharareh Adeli, Ilona Telefus Goldfarb, Michala R. Sawyer & Mark Phillippe

  2. Division of Maternal-Fetal Medicine, Tufts Medical Center, 800 Washington Street, Box 360, Boston, MA, 02111, USA

    Ingrid Liff

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  1. Ingrid Liff
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  2. Sharareh Adeli
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  3. Ilona Telefus Goldfarb
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  4. Michala R. Sawyer
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  5. Mark Phillippe
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Correspondence to Ingrid Liff.

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Institutional Animal Care and Use Committee (IACUC) approved animal research protocol: 2014 N000219 https://iacuc.hms.harvard.edu/

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Liff, I., Adeli, S., Goldfarb, I.T. et al. Modulation of IL10 and Its Receptor Subunits in Normal and Progesterone-Prolonged Gestation in the Mouse. Reprod. Sci. 27, 555–560 (2020). https://doi.org/10.1007/s43032-019-00022-7

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  • DOI: https://doi.org/10.1007/s43032-019-00022-7

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