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Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois 60612
ABSTRACT
Interleukin 11 receptor alpha (Il11ra) null mice are infertile due to defective decidualization and abnormal trophoblast invasion. We have previously shown in these mice that downregulation of decidual proteinase inhibitors plays a role in uncontrolled trophoblast invasion. However, the decidua is abnormally smaller in pseudopregnant Il11ra null mice, where trophoblast invasion is not a factor. Here, we examined whether defective decidualization is due to dysregulation of key molecules involved in decidual cell growth and differentiation. We found a dramatic downregulation of cyclin D3 in Il11ra null mice. We also found that IL11 robustly stimulates the expression of cyclin D3 in cell culture. CDK4 and CDK6, known partners of cyclin D3, are not affected. Immunolocalization studies show absence of cyclin D3 in the mesometrial site and absence of differentiated polyploid cells in the antimesometrial site of Il11ra null mice. We also examined the expression of cell differentiation factors CDKN1A (p21) and CDKN1B (p27), and found that in both in vivo and cell culture the expression of CDKN1A (p21) but not CDKN1B (p27) is under the control of IL11. Another clear target of IL11 in the decidua is BIRC5 (Survivin), whose expression is repressed in the decidua of Il11ra null mice and stimulated by IL11 in cell culture. Taken together, these results provide, at least in part, an explanation for the defective small decidua of mice lacking the Il11ra gene, and reveal for the first time that cyclin D3, CDKN1A (p21), and BIRC5 (Survivin) are targets of IL11 in the decidua.
CDKN1A, cyclin D3, deciduas, IL11, implantation
3These authors contributed equally to this work.
4Current address: Departments of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40536.
1Supported by National Institutes of Health grants HD12356, U54 HD40093, and HD 11119.
Correspondence: 2Geula Gibori, Department of Physiology and Biophysics (M/C 901), University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612. FAX: 312 413 0159; e-mail: ggibori{at}uic.edu
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