Expressional and epigenetic alterations of placental serine protease inhibitors: SERPINA3 is a potential marker of preeclampsia.
Preeclampsia is the major pregnancy-induced hypertensive disorder. It modifies the expression profile of placental genes, including several serine protease inhibitors (SERPINs). The objective of this study was to perform a systematic expression analysis of these genes in normal and pathological placentas and to pinpoint epigenetic alterations inside their promoter regions. Expression of 18 placental SERPINs was analyzed by quantitative RT-PCR on placentas from pregnancies complicated by preeclampsia, intrauterine growth restriction, or both and was compared with normal controls. SERPINA3, A5, A8, B2, B5, and B7 presented significant differences in expression in >or=1 pathological situation. In parallel, the methylation status of the CpG islands located in their promoter regions was studied on a sample of control and preeclamptic placentas. Ten SERPIN promoters were either totally methylated or totally unmethylated, whereas SERPINA3, A5, and A8 presented complex methylation profiles. For SERPINA3, the analysis was extended to 81 samples and performed by pyrosequencing. For the SERPINA3 CpG island, the average methylation level was significantly diminished in preeclampsia and growth restriction. The hypomethylated CpGs were situated at putative binding sites for developmental and stress response (hypoxia and inflammation) factors. Our results provide one of the first observations of a specific epigenetic alteration in human placental diseases and provide new potential markers for an early diagnosis.
Chelbi
Sonia T
ST
Equipe 21, Génomique et Epigénétique des Pathologies Placentaires, Unité INSERM 567/UMR Centre National de la Recherche Scientifique 8104, Université Paris V IFR Alfred Jost, Faculté de Médecine, Cochin-Port-Royal, Paris, France.
Mondon
Françoise
F
Jammes
Hélène
H
Buffat
Christophe
C
Mignot
Thérèse-Marie
TM
Tost
Jorg
J
Busato
Florence
F
Gut
Ivo
I
Rebourcet
Régis
R
Laissue
Paul
P
Tsatsaris
Vassili
V
Goffinet
François
F
Rigourd
Virginie
V
Carbonne
Bruno
B
Ferré
Françoise
F
Vaiman
Daniel
D
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D010922:Placenta Diseases / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; C516148:SERPINA3 protein, human; D015842:Serine Proteinase Inhibitors; D015843:Serpins