Endometriosis also affects the decidua in contact with the fetal membranes during pregnancy

STUDY QUESTION: Are the fetal membranes of women affected with endometriosis similar to those from disease-free women? SUMMARY ANSWER: Decidua of women with endometriosis is able to generate endometriotic-like lesions in contact with the fetal membranes. WHAT IS KNOWN ALREADY: Eutopic endometrium of women affected with endometriosis presents compromised properties. Endometrium undergoes decidualisation to accept and to further control the conceptus development during pregnancy. Decidualized endometrium is in close contact with the chorionic membrane and forms the choriodecidual layer, a major maternal-fetal interface. STUDY DESIGN, SIZE, DURATION: This is a laboratory case-control study involving diseased versus control samples. Eleven case samples and 11 control samples were collected from women in a tertiary care/research center between November 2011 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were consecutive pregnant women affected with confirmed endometriosis and disease free women, who underwent Cesarean section before labor for obstetrical indication. The choriodecidual tissues were characterized using histology, immunohistochemistry, transcriptomic and whole genome CpG methylation analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We demonstrate for the first time the presence of endometriotic-like lesions within the decidual side of the choriodecidua of the fetal membranes from women affected with severe endometriosis. Fetal membranes from women affected with endometriosis exhibited glandular components in the choriodecidual layer surrounded by enlarged decidualized cells disseminated along the entire membrane surface. Significant deregulation (variation of expression >= 2, P-value <= 0.05) was observed for 2773 genes known to be enriched in processes involved in glandular function, endocrine and nervous system, neoangiogenesis, and autoimmune disease. CpG methylation analysis revealed 5999 differentially methylated regions with a P-value <= 0.05. LIMITATIONS, REASONS FOR CAUTION: We studied women who delivered at term by Cesarean section before labor, following an uneventful pregnancy. Notwithstanding this, one cannot exclude that the presence of disseminated endometriotic lesions within the choriodecidual layer of the fetal membranes may disturb the anatomical integrity and/or the function of the membranes in some women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our results shed new light on the capability of the diseased decidua to develop lesions not only at ectopic autologous locations, but also on the semi-allogenous fetal membranes, a particularly immunotolerant environment.