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.