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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.

SUBMITTER: Ticconi C

PROVIDER: S-EPMC6862690 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Endometrial Immune Dysfunction in Recurrent Pregnancy Loss.

Ticconi Carlo C Pietropolli Adalgisa A Di Simone Nicoletta N Piccione Emilio E Fazleabas Asgerally A

International journal of molecular sciences 20191026 21

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 betw ...[more]

PMID: 31717776

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Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.

Dataset Information

Endometrial Immune Dysfunction in Recurrent Pregnancy Loss.

Publications

Endometrial Immune Dysfunction in Recurrent Pregnancy Loss.

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