title: Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2.
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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USA. Virginia.Winn@ucdenver.edu
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Winn
authors.forename: Matthew
authors.initials: M
authors.lastname: Gormley
authors.forename: Agnes C
authors.initials: AC
authors.lastname: Paquet
authors.forename: Kasper
authors.initials: K
authors.lastname: Kjaer-Sorensen
authors.forename: Anita
authors.initials: A
authors.lastname: Kramer
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Rumer
authors.forename: Ronit
authors.initials: R
authors.lastname: Haimov-Kochman
authors.forename: Ru-Fang
authors.initials: RF
authors.lastname: Yeh
authors.forename: Michael T
authors.initials: MT
authors.lastname: Overgaard
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008431:Maternal-Fetal Exchange / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017931:DNA Primers; D037102:Lectins; C120775:SIGLEC6 protein, human; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A