title: Progressive development of endometriosis and its hindrance by anti-platelet treatment in mice with induced endometriosis.
abstract: We have recently shown that platelets drive smooth muscle metaplasia (SMM) and fibrogenesis in endometriosis through epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). To see whether this is true in vivo, this prospective, randomized, and serially evaluated mouse investigation was conducted. Endometriosis was induced in female Balb/C mice, which were then randomly divided into two groups: Tanshinone IIA (TAN) and control (CTL) groups. TAN mice were treated with TAN but CTL mice received none. Every week until the 6th week after induction, five mice from each group were killed. Lesion weight was measured and lesion samples were subjected to immunohistochemistry and histochemistry analysis of platelet aggregation (CD41), E-cadherin, TGF-β1, phosphorylated Smad3, α-SMA, collagen I, CCN2, LOX, desmin and SM-MHC, and the extent of fibrosis was evaluated by Masson trichrome staining. It was found that endometriotic lesions exhibited progressive cellular changes consistent with the progressive EMT, FMT, SMM, and fibrogenesis. TAN treatment resulted in significant hindrance of EMT, FMT, SMM and fibrogenesis, and reduced lesion weight (all P-values <0.05). These data corroborate the notion that endometriotic lesions undergo progressive EMT and FMT, giving rise to SMM and ultimately fibrosis. This understanding sheds new light onto the natural history of endometriosis.
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
authors.forename: Xishi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China. Electronic address: hoxa10@outlook.com.
authors.forename: Sun-Wei
authors.initials: SW
authors.lastname: Guo
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology; D002454:Cell Differentiation; D004715:Endometriosis / Q000139:chemically induced* / Q000503:physiopathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000473:pathology; D058628:Myofibroblasts / Q000166:cytology; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D011446:Prospective Studies; D011897:Random Allocation
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: endometriosis; epithelial-mesenchymal transition; fibroblast-to-myofibroblast transdifferentiation; fibrosis; platelet; smooth muscle metaplasia