title: Effect of a dienogest for an experimental three-dimensional endometrial culture model for endometriosis.
abstract: The pathogenesis of endometriosis remains poorly understood at least in part because early stages of the disease process are difficult to investigate. Previous studies have proposed a three-dimensional fibrin matrix culture model to study human endometriosis. We examined the ultrastructural features of the endometriosis in this model and assessed the effect of a progestin on endometrial outgrowth and apoptosis in this culture system. Endometrial explants were placed in three-dimensional fibrin matrix culture and treated with and without various concentrations of the progestin dienogest. By the second week, endometrial gland-like formation was established in outgrowths both attached to and at a distance from the explants. These cells formed a combination of clumps and tubular monolayers surrounding a central cavity. Electron microscopy demonstrated that these cells are polarized with microvilli on the apical surface, desmosome-like structures, and basement membrane; features consistent with glandular epithelial cells. Outgrowth of endometrial stromal cells and glandular formation was impaired in response to dienogest in a dose-dependent manner. Our study shows that the human endometrial explants cultured in three-dimensional fibrin matrix establish outgrowths that ultrastructurally resemble ectopic endometrial implants. This model may provide insight into the cellular processes leading to endometriosis formation and enables screening of therapeutic compounds.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, Japan.
authors.forename: Japarath
authors.initials: J
authors.lastname: Prechapanich
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kajihara
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujita
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sato
authors.forename: Satomi
authors.initials: S
authors.lastname: Uchino
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Masumi
authors.initials: M
authors.lastname: Akita
authors.forename: Masabumi
authors.initials: M
authors.lastname: Nagashima
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishihara
mesh_terms: D000328:Adult; D017209:Apoptosis; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D004715:Endometriosis / Q000473:pathology*; D004717:Endometrium / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D006727:Hormone Antagonists; C023635:dienogest; D009277:Nandrolone