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This Article Full Text Full Text (PDF) All Versions of this Article: 75/1/75    most recent biolreprod.105.047647v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hewitt, D. P. Articles by Waddell, B. J. Search for Related Content PubMed PubMed Citation Articles by Hewitt, D. P. Articles by Waddell, B. J. Agricola Articles by Hewitt, D. P. Articles by Waddell, B. J.

Placental Expression of Secreted Frizzled Related Protein-4 in the Rat and the Impact of Glucocorticoid-Induced Fetal and Placental Growth Restriction

School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia 6009, Australia

ABSTRACT

Wnt genes regulate a diverse range of developmental processes, including placental formation. Activation of the WNT pathway results in translocation of beta-catenin (CTNNB1) into the nucleus and the subsequent activation of transcription factors that promote proliferation. The secreted frizzled related proteins (SFRPs) are thought to inhibit WNT signaling by binding to the WNT ligand or its frizzled receptor. In this study, we compared the expression patterns of one of these secreted molecules, SFRP4, in the two morphologically and functionally distinct regions of the rat placenta during the last third of pregnancy. In addition, we assessed whether placental SFRP4 expression is altered in a model of glucocorticoid-induced placental growth restriction. Temporal analyses of the rat placenta by quantitative RT-PCR, in situ hybridization, and immunohistochemistry during the final third of pregnancy demonstrated elevated levels of Sfrp4 mRNA and SFRP4 protein near term, specifically in trophoblast cells of the basal zone. This increase in expression of SFRP4 in basal zone trophoblasts was associated with a reduction in CTNNB1 nuclear translocation, consistent with inhibition of the WNT pathway. Maternal dexamethasone treatment (1 µg/ml of drinking water, Days 13–22), which has previously been shown to reduce placental growth, further increased the expression of Sfrp4 mRNA in both the basal and labyrinth zones of the placenta at Day 22. Collectively, these data demonstrate that increased expression of SFRP4 is associated with reduced growth of placental regions in normal pregnancy and after glucocorticoid-induced growth retardation. These observations, together with associated changes in CTNNB1 localization, support the hypothesis that increased placental expression of SFRP4 inhibits the WNT pathway and thereby influences placental growth via effects on cell fate signaling.

apoptosis, b-catenin, glucocorticoid, growth retardation, placenta, syncytiotrophoblast, trophoblast, SFRP4, WNT

¹ Correspondence: Brendan J. Waddell, School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. FAX: 61 8 6488 1051; bwaddell{at}anhb.uwa.edu.au

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