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Significance of IGFBP-4 in the Development of Fetal Growth Restriction.
MedLine Citation:
PMID:  22689691     Owner:  NLM     Status:  Publisher    
Background:Fetal growth restriction (FGR) is a leading cause of perinatal mortality and morbidity. Animal studies suggest dysregulation of IGF-binding protein (IGFBP)-4 is significant in the development of FGR, although human data are lacking. We postulated that IGFBP-4 is expressed at the maternal fetal interface and plays a role in regulating IGF bioavailability. Thus, maternal serum levels of IGFBP-4 may be associated with complications of abnormal placental growth and development including FGR.Methods:Circulating levels of IGFBP-4 and its protease, pregnancy-associated plasma protein-A (PAPP-A), were examined in healthy pregnancies. Their expression in villi and bed as possible sources of the circulating products were examined by immunohistochemistry. From the large Ottawa and Kingston (OaK) Birth Cohort, a nested case-control study was conducted to examine circulating levels of IGBP-4, PAPP-A, IGF-I, and IGF-II by Western blot in early gestation in 36 women who went on to develop FGR and 36 controls having normal-weight babies.Results:IGFBP-4 was elevated in early pregnancy compared with nonpregnant women and women in later pregnancy, consistent with the presence of abundant extravillous trophoblasts and decidual cells that highly expressed IGFBP-4. High expression of PAPP-A was observed in extravillous trophoblasts and decidual cells in early pregnancy but hardly detectable in the circulation at this time, suggesting maternal circulating PAPP-A originates more likely from syncytiotrophoblasts. Increased IGFBP-4 in the maternal circulation in early pregnancy was associated with the development of FGR [0.48 (0.28-0.74) in control vs. 1.22 (0.66-1.65) in FGR; odds ratio = 22 (95% confidence interval = 2.7-181)]. No difference was observed in circulating PAPP-A, IGF-I and IGF-II in the FGR vs. control group.Conclusion:Our findings support the role of IGFBP-4 in regulating IGF bioavailability and provide new clues for the prevention and treatment of FGR, raising the possibility of clinical use of IGFBP-4 as an early biomarker for this condition.
Qing Qiu; Mike Bell; Xiaoyin Lu; Xiaojuan Yan; Marc Rodger; Mark Walker; Shi-Wu Wen; Shannon Bainbridge; Hongmei Wang; Andree Gruslin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-11
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Chronic Disease (Q.Q., A.G.) and Clinical Epidemiology Program (M.M., M.W., S.-W.W.), Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1Y 4E9; Departments of Obstetrics and Gynaecology (A.G., M.R., M.W., S.-W.W.), Cellular and Molecular Medicine (A.G., Q.Q.), Epidemiology and Community Medicine (S.-W.W.), and Interdisciplinary School of Health Sciences (S.B.), University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada K1H 8L6; State Key Laboratory of Reproductive Biology (X.L., H.W.), Institute of Zoology, Chinese Academy of Science, Beijing, China 100101; and Departments of Obstetrics and Gynaecology (X.Y.), Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China, 050051.
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