title: Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR.
abstract: Human placental villi are surfaced by an outer multinucleated syncytiotrophoblast and underlying mononucleated cytotrophoblasts. Conflicting data have attributed one, or the other, of these villous trophoblast phenotypes to undergo enhanced apoptosis in complicated pregnancies, compared to term, normotensive pregnancies. We use high-resolution confocal microscopy after co-staining for E-cadherin, as a trophoblast plasma membrane marker, and for the cleavage products of cytokeratin 18 and PARP1, as markers for caspase-mediated apoptosis, to distinguish between apoptotic cytotrophoblasts and apoptosis within the syncytiotrophoblast. We test the hypothesis that increased caspase-mediated apoptosis occurs in villi of placentas derived from pregnancies complicated by preeclampsia, intrauterine growth restriction (IUGR), or both. We find significantly elevated apoptosis in villous cytotrophoblasts from women with preeclampsia and/or IUGR, compared to term, normotensive pregnancies. Apoptosis of cytotrophoblasts in villi from complicated pregnancies appears to progress similarly to what we found previously for apoptotic cytotrophoblasts in villi from in term, normotensive pregnancies. Notably, caspase-mediated apoptosis was not detectable in regions with intact syncytiotrophoblast, suggesting strong repression of apoptosis in this trophoblast phenotype in vivo. We suggest that the elevated apoptosis in cytotrophoblasts in preeclampsia contributes to the placental dysfunction characteristic of this disorder. We also propose that repression of apoptosis in the syncytiotrophoblast is important to prevent apoptosis sweeping throughout the syncytium, which would result in widespread death of this essential interface for maternal-fetal exchange.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, Campus Box 8064, 4566 Scott Ave., St. Louis, MO 63110, USA. longtine@wudosis.wustl.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Longtine
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: A O
authors.initials: AO
authors.lastname: Odibo
authors.forename: Y
authors.initials: Y
authors.lastname: Zhong
authors.forename: D M
authors.initials: DM
authors.lastname: Nelson
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D011225:Pre-Eclampsia / Q000201:enzymology / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000473:pathology*
chemical_list: D020169:Caspases