Defective production of interleukin-11 by decidua and chorionic villi in human anembryonic pregnancy

Previous study demonstrated that IL-11 receptor a knockout female mice (IL-11Ralpha(-/-)) were phenotypically normal but infertile due to defective decidualization. However, the role of IL-11. signaling in human reproduction remains unclear. This study examined the expression of IL-11, IL-11Ralpha, and signal transduction factor glycoprotein 130 in different phases of endometrium (six in proliferative phase and four in secretory phase), and the decidua and villi of normal pregnancy (NP; n = 25) and anembryonic pregnancy (AP; n = 25) in the first trimester (gestational week 7-9). RT-PCR showed IL-11, IL-11Ralpha, and glycoprotein 130 mRNA expression in all samples, except the absence of IL-11 signal in the unstimulated MRC-5 cell and the proliferative phase endometrium. Real-time quantitative PCR showed that the relative level of IL-11Ralpha mRNA was not significantly different among proliferative phase endometrium (relative level; mean +/- SEM, 1.4 +/- 0.5), secretory phase endometrium (1.3 +/- 0.1), or decidua from NP or AP (1.7 +/- 0.3 and 1.9 +/- 0.4, respectively), but was significantly greater in chorionic villi either from NP or AP (7.6 +/- 1.3 and 10.6 +/- 1.9, respectively; both P < 0.05, compared with decidua or endometrium). No difference of IL-11Ralpha mRNA level was found between NP and AP (1.7 +/- 0.3 vs. 1.9 +/- 0.4 in deciduas; 7.6 +/- 1.3 vs. 10.6 +/- 1.9 in villi; both P > 0.05). In situ hybridization localized IL-11Ralpha mRNA expression in proliferative phase endometrium (stroma only), secretory phase endometrium (stroma and gland), decidua (stroma and gland), and villi (trophoblast and stroma). The staining intensities were not distinctly different between different groups of samples or between different cell types in a sample. No difference in IL-11Ralpha expression was found between NP and AP when either decidua or chorionic villi was analyzed. IL-11 mRNA level was not detected in the proliferative phase (relative level, 0.0 +/- 0.0), was barely detectable in the secretory phase (0.03 +/- 0.02), and was significantly increased in decidua (1.7 +/- 0.2 and 0.1 0.1, respectively, for NP and AP) and chorionic villi (13.0 +/- 2.2 and 0.2 +/- 0.1). In addition, IL-11 mRNA level was higher in NP than in AP both in decidua (1.7 0.2 vs. 0.1 0.1; P = 0.03) and in villi (13.0 +/- 2.2 vs. 0.2 +/- 0.1; P < 0.001). Immunohistochemistry study showed that IL-11 was nearly absent in endometrium in both phases, but clearly detectable in decidua and villi. Consistent with the results of quantitative PCR, the staining intensity was stronger in villi and decidua from NP than those from AP. The spatial and temporal changes in IL-11 and its receptor observed in this study suggest that IL-11 may be produced both by the embryo (predominantly) and the decidual cells and exerts its action on chorionic villi and decidua in an autocrine or paracrine manner. In the presence of a baseline level of IL-11Ralpha, IL-11 may subsequently regulate placentation and decidualization for the maintenance of a NP. The finding of decreased IL-11 expression in the absence of any change in IL-11Ralpha in AP suggests that defective expression of IL-11 but not IL-11Ralpha may account for certain cases of AP.