L Marcellin1, P Santulli2, J Gogusev3, C Lesaffre4, S Jacques4, C Chapron2, F Goffinet5, D Vaiman3, C Méhats3. 1. Cochin Institute, Inserm U1016, CNRS 8104, Université Paris Descartes, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Port Royal - Hôpitaux Universitaires Paris Centre, Service de Gynécologie-Obstétrique II et Médecine de la Reproduction, Paris, France Université Paris Descartes, DHU Risques et Grossesse, Paris, France louismarcellin@gmail.com. 2. Cochin Institute, Inserm U1016, CNRS 8104, Université Paris Descartes, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Port Royal - Hôpitaux Universitaires Paris Centre, Service de Gynécologie-Obstétrique II et Médecine de la Reproduction, Paris, France. 3. Cochin Institute, Inserm U1016, CNRS 8104, Université Paris Descartes, Paris, France Université Paris Descartes, DHU Risques et Grossesse, Paris, France. 4. Cochin Institute, Inserm U1016, CNRS 8104, Université Paris Descartes, Paris, France. 5. Université Paris Descartes, DHU Risques et Grossesse, Paris, France Université Paris Descartes, Faculté de Médecine, AP- HP, Groupe Hospitalier Universitaire Ouest, Centre Hospitalier Universitaire Cochin Broca Hôtel Dieu, Port Royal Maternity, Department of Gynecology Obstetrics I, Paris, France.
Abstract
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.
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.
Authors: Silvia Vannuccini; Vicki L Clifton; Ian S Fraser; Hugh S Taylor; Hilary Critchley; Linda C Giudice; Felice Petraglia Journal: Hum Reprod Update Date: 2015-09-22 Impact factor: 15.610
Authors: Louis Marcellin; Francois Goffinet; Elie Azria; Anne Thomin; Charles Garabedian; Jeanne Sibiude; Eric Verspyck; Martin Koskas; Pietro Santulli; Jessica Rousseau; Pierre-Yves Ancel; Charles Chapron Journal: JAMA Netw Open Date: 2022-02-01
Authors: Fatima Barragan; Juan C Irwin; Shaina Balayan; David W Erikson; Joseph C Chen; Sahar Houshdaran; Terhi T Piltonen; Trimble L B Spitzer; Ashley George; Joseph T Rabban; Camran Nezhat; Linda C Giudice Journal: Biol Reprod Date: 2016-04-13 Impact factor: 4.285
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