Document Detail

Failure of decidual arteriolar remodeling in the CBA/J x DBA/2 murine model of recurrent pregnancy loss is linked to increased expression of tissue inhibitor of metalloproteinase 2 (TIMP-2).
MedLine Citation:
PMID:  16389019     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Uterine vascular remodeling at mid gestation includes the thinning of the vessel walls and, typically, an increase in lumen diameter. This study aimed to elucidate any differences in structural remodeling in normal murine pregnancies versus those differences that resulted from the crossing of CBA/J female mice by DBA/2 male mice, a combination that is known to exhibit recurrent resorption/pregnancy loss. STUDY DESIGN: CBA/J female mice that were pregnant by DBA/2 male mice (abnormals) and DBA/2 female mice that were pregnant by CBA/J male mice (normals) were killed at mid gestation, which is a time when fetal resorption can be identified. Tissues were collected for permanent fixation and gene expression studies with complementary DNA macroarrays that were specific for extracellular matrix proteins. A 2-fold increase in expression or a 50% decline was considered significant. Expression changes were confirmed by real-time reverse transcriptase-polymerase chain reaction. RESULTS: The vessel-to-lumen diameter ratios were found to be significantly greater for the CBA/J implantation sites (1.50 +/- 0.05 vs 1.22 +/- 0.02, respectively; P < .0001), which indicates a lack of vascular remodeling. There was also a trend towards smaller lumen diameters for the CBA/J vessels, but this was not statistically significant (78.2 +/- 4.4 microm vs 93.5 +/- 6.8 microm, respectively; P = .22). The mean coefficient of variation for lumen measurements was 0.8% and for vessel diameter was 0.3%. The ranges were 0 to 3.2% and 0 to 1.4%, respectively. Tissue inhibitor of metalloproteinase 2 expression was up-regulated in the placentas of the group with higher resorption rates when compared with normals. This was confirmed with reverse transcriptase-polymerase chain reaction, where abnormals exhibited 2.6-fold greater tissue inhibitor of metalloproteinase 2 protein quantities when compared with normal controls (P = .03). CONCLUSION: The expansive vascular remodeling of decidual vessels that is characteristic of normal murine pregnancy is attenuated significantly in the CBA/J x DBA/2 mating combination, which is known for its tendency to recurrent fetal resorption. This has been correlated with a relative overexpression of tissue inhibitor of metalloproteinase 2 protein in placentas of this strain combination and compared with normals.
Marjorie E Dixon; Edward K Chien; George Osol; Peter W Callas; Elizabeth A Bonney
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  194     ISSN:  1097-6868     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-03     Completed Date:  2006-04-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  113-9     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, University of Vermont, Burlington, VT 05405, USA.
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MeSH Terms
Arterioles / physiopathology*
Decidua / blood supply*
Fetal Resorption / metabolism,  pathology,  physiopathology*
Gene Expression Profiling
Mice, Inbred CBA*
Mice, Inbred DBA*
Oligonucleotide Array Sequence Analysis
Placenta / metabolism,  pathology
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-2 / genetics,  metabolism*
Reg. No./Substance:
0/RNA, Messenger; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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