title: Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early postnatal uterine development.
abstract: Postnatal uterine development is marked by periods of tissue remodeling. The objective of the present study was to examine the role of tissue inhibitor of metalloproteinase-1 (TIMP-1), a regulator of tissue remodeling events, during postnatal uterine development and to assess the phenotypic consequences of disruption of the TIMP-1 gene product during this time period. To accomplish this goal, wild-type and TIMP-1 null mice were sacrificed at Postnatal Days (PNDs) 5, 10, 15, 20, and 25 and uterine morphology, TIMP expression and matrix metalloproteinase (MMP) activity were assessed. In wild-type mice, TIMP-1 mRNA steady-state levels were highest at PND 5, after which expression decreased. TIMP-2 and TIMP-3 expression in wild-type mice showed no significant changes from PND 5 to 25. In TIMP-1 null mice, TIMP-2 and TIMP-3 expression patterns were similar to those in wild-type counterparts with the exception that, at PND 10, TIMP-2 and TIMP-3 expression was significantly lower in the null mice. Endometrial gland number and uterine histology were similar between genotypes at PNDs 5 and 10, but at PNDs 15 and 20, endometrial glands were more abundant in TIMP-1 null mice. Associated with the increased gland density in the null mice was an increase in total MMP activity above the levels expressed in wild-type mice. In summary, disruption of the TIMP-1 gene product is associated with reduced TIMP-2 and TIMP-3 steady-state mRNA levels, elevated MMP activity, and accelerated endometrial gland formation. We conclude that, during early postnatal uterine development, TIMP-1 may be critical for proper endometrial gland development.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Basic and Clinical Women's Research, University of Kansas School of Medicine, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Han-E
authors.initials: HE
authors.lastname: Zhou
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Warren B
authors.initials: WB
authors.lastname: Nothnick
mesh_terms: D000818:Animals; D004717:Endometrium / Q000033:anatomy & histology / Q000254:growth & development* / Q000502:physiology*; D005088:Exocrine Glands / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2