Specific isoforms of leucine-rich α2-glycoprotein detected in the proliferative endometrium of women undergoing assisted reproduction are associated with spontaneous pregnancy

Abstract

To examine differences in specific protein expression from the surface of the human endometrium with respect to eventual pregnancy in infertile women. Laboratory study. University hospital. Thirty-one women presenting for investigation into infertility at an assisted reproductive unit. Endometrial flushings were collected during the proliferative phase of the menstrual cycle and subjected to electrophoretic separation on the basis of isoelectric point and molecular weight. Computerized analysis of the resulting spots was performed, and the proteins were identified using tandem mass spectrometry. The expression of individual isoforms of leucine-rich alpha2-glycoprotein (LRG) was compared in nonpregnant patients (n = 25), those who became pregnant as a result of treatment (n = 3), and those who had treatment-independent pregnancies (n = 3). A statistically significant difference was found in expression of two LRG isoforms, which were higher in the women who subsequently became pregnant independent of treatment. Several indirect lines of evidence suggest a role for LRG in implantation/decidualization. [1] LRG is implicated in transforming growth factor beta signal transduction. [2] Similar sequences have been identified in murine uterine tissues. [3] LRG may be involved in the infiltration of decidua by uterine natural killer cells, given that the murine homolog of LRG supports lymphocyte infiltration into secondary lymphoid tissues. [4] Human uterine natural killer cells differentiate into granular forms during early pregnancy, and LRG is known to support neutrophil granulocytic differentiation in humans.