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Two Methods for Establishing Primary Human Endometrial Stromal Cells from Hysterectomy Specimens
Published on: May 23, 2014
The production of interleukin-11 and decidualization are compromised in endometrial stromal cells derived from
Natalia Karpovich1, Petra Klemmt, Jung Hye Hwang
1Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Abstract:
IL-11 signaling is critical for decidualization of the endometrial stroma in early pregnancy in the mouse. In this study, we investigate the function of IL-11 signaling in cAMP-induced decidualization of human endometrial stromal cells. We show that treatment of endometrial stromal cells with 8-bromo-cAMP (8-Br-cAMP) results in an increase in the levels of secreted IL-11, whereas levels of cell surface IL-11 receptor alpha are similar with or without 8-Br-cAMP treatment. The production of IL-11 correlates with the production of molecular markers of decidualization, prolactin and IGF-binding protein-1. The expression of these markers is inhibited when IL-11 signaling is specifically blocked in decidualizing endometrial stromal cells by the IL-11 antagonist W147A. We demonstrate that 8-Br-cAMP-induced endometrial stromal cells derived from patients with primary infertility produce lower levels of prolactin, IGF-binding protein-1, and IL-11 than cells derived from fertile women. Our results suggest that IL-11 expression is critically important during decidualization in the human endometrium, and that aberrant regulation of endometrial IL-11 production may be associated with some types of infertility.
Insights
Interleukin-11 (IL-11) signaling is vital for human endometrial decidualization. Impaired IL-11 production in women with infertility suggests a link between IL-11 and reproductive health.
Area of Science:
- Reproductive Biology
- Cell Signaling
- Endocrinology
Background:
- Decidualization is essential for early pregnancy establishment.
- Interleukin-11 (IL-11) signaling plays a known role in mouse decidualization.
- The role of IL-11 in human endometrial decidualization remains to be fully elucidated.
Purpose of the Study:
- To investigate the function of IL-11 signaling in cAMP-induced decidualization of human endometrial stromal cells.
- To determine if IL-11 production is altered in women with primary infertility.
Main Methods:
- Human endometrial stromal cells were treated with 8-bromo-cAMP (8-Br-cAMP) to induce decidualization.
- IL-11 and IL-11 receptor alpha levels were measured.
- Decidualization markers (prolactin, IGF-binding protein-1) were assessed.
- IL-11 signaling was blocked using an IL-11 antagonist (W147A).
Main Results:
- cAMP treatment increased secreted IL-11 levels but not IL-11 receptor alpha.
- IL-11 production correlated with decidualization markers.
- Blocking IL-11 signaling inhibited decidualization markers.
- Cells from infertile women showed reduced production of IL-11 and decidualization markers.
Conclusions:
- IL-11 signaling is critical for human endometrial decidualization.
- Aberrant IL-11 production may contribute to certain types of infertility.
- Targeting IL-11 pathways could offer therapeutic potential for infertility.
