title: Homocysteine induces trophoblast cell death with apoptotic features.
abstract: Hyperhomocysteinemia has been suggested as a possible risk factor in women suffering from habitual abortions, placental abruption or infarcts, preeclampsia, and/or intrauterine growth retardation. However, little is known about the pathogenic mechanisms underlying the action of homocysteine. The present study investigated the in vitro ability of homocysteine to affect trophoblast gonadotropin secretion and to induce cell death. In primary human trophoblast cells, homocysteine treatment (20 micromol/L) resulted in cellular flattening and enlargement, extension of pseudopodia, and cellular vacuolization. Cellular detachment, apoptosis, and necrosis were favored. With in situ nick end labeling, we investigated DNA degradation, and we used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Cytochrome c release from mitochondria to the cytosol and DNA cleavage in agarose gel have been investigated. Homocysteine, but not cysteine, induced trophoblast apoptosis and significantly reduced human chorionic gonadotropin secretion. These findings suggest that trophoblast cell death might represent a pathogenic mechanism by which homocysteine may cause pregnancy complications related to placental diseases.
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, 00168 Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Di Simone
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggiano
authors.forename: Dario
authors.initials: D
authors.lastname: Caliandro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Riccardi
authors.forename: Antonella
authors.initials: A
authors.lastname: Evangelista
authors.forename: Brigida
authors.initials: B
authors.lastname: Carducci
authors.forename: Alessandro
authors.initials: A
authors.lastname: Caruso
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D006710:Homocysteine; D045304:Cytochromes c; D020169:Caspases