Host-derived TGFB1 deficiency suppresses lesion development in a mouse model of endometriosis.
Transforming growth factor-β1 (TGFB1) is a multifunctional cytokine that is abundant in both endometriotic lesions and the peritoneal fluid in women with endometriosis. However, the role of TGFB1 in the development of endometriosis is as yet undefined. In the present study, we investigated the physiologic function of TGFB1 in endometriotic lesion development, using Tgfb1-null mutant mice on a background of severe combined immunodeficiency. Xenotransplantation of human eutopic endometrial tissue resulted in development of endometriosis-like lesions in 63% of ovariectomized estrogen-supplemented Tgfb1-null mutant mice and in 68% of wild-type control mice. Median lesion weight was reduced by 11-fold in Tgfb1-null mice compared with wild-type control mice, and the fraction of glandular epithelium in lesions from Tgfb1-null mice was reduced by 32% compared with that in control mice. In lesions from Tgfb1-null mice, the relative abundance of both macrophages and α-smooth muscle actin-positive myofibroblasts was reduced by 66% and 47%, respectively. Deficiency of TGFB1 neither altered the percentage of proliferating cells in the epithelial or stromal compartments of the lesions nor affected blood vessel density or vessel size. Observation of this study indicates that host-derived TGFB1 deficiency suppresses endometriotic lesion development and provides proof of principle that targeting TGFB1 signaling pathways in cells that support the survival of ectopic endometrium may be an effective therapeutic approach in women with endometriosis.
The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia; Department of Obstetrics and Gynaecology, Women's and Children's Hospital, North Adelaide, Australia. Electronic address: louise.hull@adelaide.edu.au.
M Louise
ML
Hull
The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
M Zahied
MZ
Johan
Department of Obstetrics and Gynaecology, Women's and Children's Hospital, North Adelaide, Australia.
Wendy L
WL
Hodge
The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
Sarah A
SA
Robertson
The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia; School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia.
Wendy V
WV
Ingman
D000328:Adult; D000818:Animals; D049109:Cell Proliferation; D004715:Endometriosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008875:Middle Aged; D058628:Myofibroblasts / Q000473:pathology; D010052:Ovariectomy; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000502:physiology*; D014183:Transplantation, Heterologous; D055815:Young Adult
D053773:Transforming Growth Factor beta1