Unexplained habitual abortion is associated with a reduced endometrial release of soluble intercellular adhesion molecule-1 in the luteal phase of the cycle

Although the mechanisms causing recurrent spontaneous abortion (RSA) remain frequently speculative, recent evidence indicates that a specific uterine immune-endocrine network plays a pivotal role in the continuation of pregnancy. We have recently demonstrated that an adhesion molecule of the immune system, named intercellular adhesion molecule (ICAM)-1, is markedly expressed at both protein and mRNA levels in endometrial stromal cells and is able to mediate their interaction with lymphoid cells. Moreover, we have shown that the soluble form of ICAM-1 (sICAM-1) can be released by the endometrium in a hormone-dependent manner. The present study was designed to determine whether surface and/or sICAM-1 expression by cultured endometrial stromal cells could be related to early pregnancy loss in patients with a history of unexplained RSA. Luteal-phase endometrial biopsies were obtained from eight patients who had experienced three or more consecutive unexplained RSAs in the first trimester and 12 control fertile women. Surface ICAM-1 was similarly expressed on luteal-phase endometrial cells obtained from women with and without a history of unexplained RSA. In contrast, the endometrial release of sICAM-1 was significantly lower in abortion-prone patients than in control women. sICAM-1 is a cytokine-inducible molecule able to interfere with several immunological responses and the reduced levels of the protein shed by the endometrium in patients who have suffered from unexplained RSAs may reflect the presence of an altered immunological environment during the early phases of pregnancy.