1. Pathogenesis of endometriosis: the genetic/epigenetic theory
- Author
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Leila Adamyan, Victor Gomel, Dan C. Martin, Anastasia Ussia, Arnaud Wattiez, and Philippe R. Koninckx
- Subjects
DEEP ENDOMETRIOSIS ,Genetic Markers ,Infertility ,Pathology ,medicine.medical_specialty ,Heredity ,heredity ,PROMOTER POLYMORPHISMS ,PLACENTAL PROTEIN-14 ,Endometriosis ,Disease ,Endometrium ,MESENCHYMAL STEM-CELLS ,Epigenesis, Genetic ,Menstruation ,EUTOPIC ENDOMETRIUM ,Risk Factors ,Metaplasia ,PROGESTERONE RESISTANCE ,Animals ,Humans ,Medicine ,genetics ,Genetic Predisposition to Disease ,Adenomyosis ,INFILTRATING ENDOMETRIOSIS ,PERITONEAL-FLUID ,Reproductive Biology ,Science & Technology ,epigenetics ,business.industry ,pathogenesis ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,Placentation ,IN-VITRO ,Prognosis ,medicine.disease ,MENSTRUAL DISSEMINATION ,Phenotype ,medicine.anatomical_structure ,classification ,Reproductive Medicine ,Female ,medicine.symptom ,business ,Life Sciences & Biomedicine - Abstract
OBJECTIVE: To study the pathophysiology of endometriosis. DESIGN: Overview of observations on endometriosis. SETTING: Not applicable. PATIENT(S): None. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): The hypothesis is compatible with all observations. RESULT(S): Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases. CONCLUSION(S): The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed. ispartof: FERTILITY AND STERILITY vol:111 issue:2 pages:327-340 ispartof: location:United States status: published
- Published
- 2019