This Article Full Text Full Text (PDF) All Versions of this Article: 90/1/379    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, A. G. Articles by Westwood, M. Search for Related Content PubMed PubMed Citation Articles by Miller, A. G. Articles by Westwood, M. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy Related Collections Female Endocrinology

Adenovirally Mediated Expression of Insulin-Like Growth Factors Enhances the Function of First Trimester Placental Fibroblasts

Endocrine Sciences (A.G.M., M.W.) and Academic Unit of Obstetrics and Gynecology (A.G.M., J.D.A.), University of Manchester, Manchester, United Kingdom M13 9PT

Address all correspondence and requests for reprints to: Dr. Melissa Westwood, Endocrine Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, United Kingdom M13 9PT. E-mail: melissa.westwood{at}manchester.ac.uk.

IGFs are critical in fetal growth because of their role in placental development and function. In this study, we used adenovirus (Ad-IGF) to deliver sense or antisense IGF-I or IGF-II cDNA to human primary placental fibroblasts (PPF) in vitro to determine whether this could lead to enhanced placental cell function. PPFs virally transfected with Ad-IGF-I or Ad-IGF-II showed 7-fold (P < 0.01) and 3-fold (P < 0.01) increases in [³H]thymidine incorporation at 48 h post infection compared with nontransfected controls. In a coculture system designed to assess cell migration, nontransfected PPF cells positioned over a monolayer transfected by Ad-IGF-I or Ad-IGF-II showed a more than 10-fold (P < 0.01) and a 7-fold (P < 0.01) increase in migration compared with cells positioned above a nontransfected monolayer. After 96 h in culture, PPFs transfected with sense Ad-IGF-I or Ad-IGF-II showed 2% apoptosis compared with 16% of nontransfected cells, whereas 37% and 25% of cells transfected with antisense Ad-IGF-I or Ad-IGF-II were apoptotic. This work has established that cells of placental origin are amenable to adenoviral transfection and that IGFs exert autocrine and paracrine effects on proliferation, migration, and survival, suggesting that enhancement of IGF levels in the placenta may augment placental function and increase fetal growth.

This article has been cited by other articles:

				K. Forbes, M. Westwood, P. N. Baker, and J. D. Aplin Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1313 - C1322. [Abstract] [Full Text] [PDF]