Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2

Virginia D Winn, Matthew Gormley, Agnes C Paquet, Kasper Kjær-Sørensen, Anita Kramer, Kristen K Rumer, Ronit Haimov-Kochman, Ru-Fang Yeh, Michael T Overgaard, Ajit Varki, Claus Oxvig, Susan J Fisher

    Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

    Abstract

    Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.
    Original languageEnglish
    JournalEndocrinology
    Volume150
    Issue1
    Pages (from-to)452-62
    Number of pages10
    ISSN0013-7227
    DOIs
    Publication statusPublished - 2008

    Keywords

    • Antigens, CD
    • Antigens, Differentiation, Myelomonocytic
    • DNA Primers
    • Female
    • Gene Expression Regulation
    • Humans
    • Lectins
    • Maternal-Fetal Exchange
    • Oligonucleotide Array Sequence Analysis
    • Pre-Eclampsia
    • Pregnancy
    • Pregnancy-Associated Plasma Protein-A

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