title: Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.
abstract: In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis.
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rockfield
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Taran
authors.affiliation: Department of Integrative Biology, University of South Florida, Tampa, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Haller
authors.affiliation: Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Engelman
authors.affiliation: Department of Basic Science-Microbiology, Ponce Health Sciences University and School of Medicine, Ponce Research Institute, Ponce, Puerto Rico.|Department of Clinical Sciences and Ob-Gyn, Ponce Health Sciences University and School of Medicine, Ponce Research Institute, Ponce, Puerto Rico.
authors.forename: I
authors.initials: I
authors.lastname: Flores
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Panina-Bordignon
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nanjundan
mesh_terms: D000818:Animals; D001343:Autophagy; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice
chemical_list: D006886:Hydroxychloroquine