Endometrial Immune Dysfunction in Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.

Keywords: decidua; endometrium; immunologic dysfunction; recurrent pregnancy loss.

Figure 1

Schematic representation of the changes occurring in the human endometrium and in local immune cell trafficking in the normal state and in recurrent pregnancy loss (RPL). (a) Endometrium in the secretory phase of the menstrual cycle in the absence of the embryo; (b) endometrium in the presence of a normally implanting embryo; (c) endometrial immune derangements in RPL. M: macrophages; uNK: uterine natural killer cell; iDC: immature uterine dendritic cell; mDC: mature uterine dendritic cell; N: neutrophil granulocyte; Treg: regulatory T cell; MC: mastocyte; Teff: effector T cells; ESC: endometrial stromal cell; BV: blood vessel.