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Effect of Prolonged In Vivo Administration of Progesterone in Pregnancy on Myometrial Gene Expression, Peripheral Blood Leukocyte Activation, and Circulating Steroid Hormone Levels

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Abstract

Objective

We aimed to investigate the effects of progesterone on gene expression and function of both myometrium and circulating leukocytes.

Methods

We recruited women participating in a randomized clinical trial of progesterone to prevent preterm delivery. These participants had a twin pregnancy and were managed in 1 of 2 tertiary referral centers. Participants were treated with progesterone (90 mg vaginally) or placebo from 24 to 34 weeks of pregnancy. The outcome measures were myometrial and leukocyte gene expression and expression of cell surface markers in circulating leukocytes, all quantified ex vivo.

Results

Prolonged in vivo administration of progesterone inhibited myometrial expression of connexins 26 and 43, endothelial nitric acid synthase (eNOS), and the prostaglandin receptor EP2 ex vivo. Administration of progesterone also increased numbers of circulating neutrophils while decreasing lymphocyte proportions and decreasing neutrophil CD11b expression.

Conclusion

The observed effects of prolonged in vivo administration of progesterone will minimize the ability of the uterus to contract as a synctium and the ability of peripheral blood leukocytes to migrate into the myometrium during parturition. We suggest that these are putative mechanisms by which progesterone might prevent preterm birth in women at high risk.

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Authors and Affiliations

  1. Centre for Reproductive Biology, Queen’s Medical Research Centre, University of Edinburgh, Edinburgh, EH16 4TY, UK

    Jane E. Norman MD, Meifang Yuan PhD, Forbes Howie PhD & Graham Harold

  2. Reproductive and Maternal Medicine, University of Glasgow, Glasgow, UK

    Laurie Anderson MD, Anne Young MSc & Fiona Jordan MSc

  3. Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre (GBRC), University of Glasgow, Glasgow, UK

    Iain McInnes PhD & Margaret M. Harnett PhD

Authors
  1. Jane E. Norman MD
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  2. Meifang Yuan PhD
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  3. Laurie Anderson MD
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  4. Forbes Howie PhD
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Correspondence to Jane E. Norman MD.

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Authors’ Note

JEN, MMH, and IBMcI received grant support for this work from January 2005 to May 2007. LA and MY had their salaries paid for by grants directly supporting this work. JEN has received honoraria from academic institutions for lectures including data from this work. This work was previously presented in abstract form

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Norman, J.E., Yuan, M., Anderson, L. et al. Effect of Prolonged In Vivo Administration of Progesterone in Pregnancy on Myometrial Gene Expression, Peripheral Blood Leukocyte Activation, and Circulating Steroid Hormone Levels. Reprod. Sci. 18, 435–446 (2011). https://doi.org/10.1177/1933719110395404

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