Conditional deletion of Sox17 reveals complex effects on uterine adenogenesis and function.
The importance of canonical Wnt signaling to murine uterine development is well established. Mouse models in which uterine-specific Wnt ligands, β-catenin, or Lef1 are disrupted result in failure of postnatal endometrial gland development. Sox17 is a transcription factor characterized in numerous tissues as an antagonist of Wnt signaling. Thus, we hypothesized that conditional ablation of Sox17 would lead to hyperproliferation of endometrial glands in mice. Contrary to our prediction, disruption of Sox17 in epithelial and stromal compartments led to inhibition of endometrial adenogenesis and a loss of reproductive capacity. Epithelium-specific Sox17 disruption resulted in normal adenogenesis although reproductive capacity remained impaired. These findings suggest that non-epithelial, Sox17-positive cells are necessary for adenogenesis and that glands require Sox17 to properly function. To our knowledge, these findings are the first to implicate Sox17 in endometrial gland formation and reproductive success. The data presented herein underscore the importance of studying Sox17 in uterine homeostasis and function.
Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Amy
A
Guimarães-Young
Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Traci
T
Neff
Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Adam J
AJ
Dupuy
Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Electronic address: michael-goodheart@uiowa.edu.
Michael J
MJ
Goodheart
D000818:Animals; D004717:Endometrium / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000502:physiology*; D005088:Exocrine Glands / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D024002:HMGB Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000096:biosynthesis / Q000235:genetics; D006706:Homeostasis; D006965:Hyperplasia; D007247:Infertility, Female / Q000235:genetics / Q000473:pathology; D008164:Luminescent Proteins / Q000032:analysis; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D055760:SOXF Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D017154:Stromal Cells / Q000502:physiology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000502:physiology
C496503:Foxa2 protein, mouse; D024002:HMGB Proteins; C497574:Lef1 protein, mouse; D008164:Luminescent Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D051542:Hepatocyte Nuclear Factor 3-beta
Adenogenesis; Development; Endometrial glands; Mouse model; Sox17; Uterus