title: ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts.
abstract: Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have been consistently associated with the subsequent development of preeclampsia and fetal growth restriction. These molecules are both metalloproteinases secreted by the placenta that cleave insulin-like growth factor binding proteins (IGFBPs), although ADAM12 also has numerous other substrates. Recent work has identified ADAM12, and particularly its shorter variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts into the lining of the uterus, a critical step in normal placental development. While the mechanisms underlying this regulation are not yet clear, they may involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or IGFs from IGFBPs. In contrast, there has been relatively little functional work examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the functions of these markers and the mechanisms underlying their association with disease could improve screening strategies and enable the development of new therapeutic interventions.
authors.affiliation: a Simon Fraser University, Biological Sciences , Burnaby , Canada.
authors.forename: Julian K
authors.initials: JK
authors.lastname: Christians
authors.affiliation: b Department of Obstetrics and Gynecology , The University of British Columbia , Vancouver , Canada.|c The Child and Family Research Institute , Vancouver , Canada.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Beristain
mesh_terms: D000072199:ADAM12 Protein / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D000072199:ADAM12 Protein; D011266:Pregnancy-Associated Plasma Protein-A
keywords: A disintegrin and metalloproteinase 12; ADAM12; PAPP-A; fetal growth restriction; invasion; preeclampsia; pregnancy-associated plasma protein-A; trophoblast