Macrophage-Derived LIF and IL1B Regulate Alpha(1,2)Fucosyltransferase 2 (Fut2) Expression in Mouse Uterine Epithelial Cells During Early Pregnancy1 (original) (raw)

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3Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

2Correspondence: Melinda J. Jasper, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide SA 5005, Australia. FAX: 61 8 83034099;

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3Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

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3Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

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3Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

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4Maternal and Fetal Health Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom

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3Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

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Revision received:

20 May 2010

Accepted:

13 September 2010

Published:

01 January 2011

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Melinda J. Jasper, Alison S. Care, Brad Sullivan, Wendy V. Ingman, John D. Aplin, Sarah A. Robertson, Macrophage-Derived LIF and IL1B Regulate Alpha(1,2)Fucosyltransferase 2 (Fut2) Expression in Mouse Uterine Epithelial Cells During Early Pregnancy, Biology of Reproduction, Volume 84, Issue 1, 1 January 2011, Pages 179–188, https://doi.org/10.1095/biolreprod.110.085399
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Abstract

Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 2.4.1.69), and Fut4 (EC 2.4.1.214) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination.

© 2011 by the Society for the Study of Reproduction, Inc.

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