title: Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome.
abstract: Antiphospholipid syndrome (APS), characterized by circulating antiphospholipid (aPL) antibodies, is a major cause of early pregnancy failure and placental insufficiency. In this study, we examined whether impaired endometrial differentiation before conception contributes to the high incidence of pregnancy complications in APS. Timed secretory endometrial biopsies were obtained from a cohort of women with recurrent pregnancy loss (RPL). Real-time quantitative (RTQ)-PCR was used to determine the expression levels of transcripts that encode for decidual markers, proinflammatory cytokines and complement regulatory proteins. Expression of decidual markers such as prolactin (PRL), tissue factor (TF) and signal transducer and activator of transcription 5 (Stat5), but not insulin-like growth factor-binding protein 1 (IGFBP-1), was significantly lower in samples obtained from aPL(+) patients (n = 24) when compared with aPL(-) group (n = 58) (P < 0.05). The abundance of transcripts encoding for interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha) or Stat1 did not differ significantly between both groups (P >/= 0.05). However, analysis of transcripts that encode for complement regulatory proteins showed a marked decrease in decay-accelerating factor (DAF/CD55) levels in aPL(+) patients (P = 0.005), which was mimicked at protein level as demonstrated by immunohistochemistry. In summary, patients with RPL have distinct endometrial gene expression profiles depending on the presence or absence of circulating aPL antibodies. In APS, impaired endometrial differentiation and lower DAF/CD55 expression before conception may compromise implantation and predispose to complement-mediated pregnancy failure.
authors.affiliation: Institute of Reproductive and Developmental Biology, Wolfson & Weston Research Centre for Family Health, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Francis
authors.forename: Raj
authors.initials: R
authors.lastname: Rai
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: Safaa
authors.initials: S
authors.lastname: El-Gaddal
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Fernandes
authors.forename: Preeti
authors.initials: P
authors.lastname: Jindal
authors.forename: Amali
authors.initials: A
authors.lastname: Lokugamage
authors.forename: Lesley
authors.initials: L
authors.lastname: Regan
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000235:genetics*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000235:genetics*; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D018957:CD59 Antigens / Q000235:genetics; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000235:genetics*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D051916:Membrane Cofactor Protein / Q000235:genetics; D011247:Pregnancy; D011388:Prolactin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013925:Thromboplastin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017152:Antibodies, Antiphospholipid; D000943:Antigens, Differentiation; D018958:CD55 Antigens; D018957:CD59 Antigens; D018970:Insulin-Like Growth Factor Binding Protein 1; D051916:Membrane Cofactor Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011388:Prolactin; D003165:Complement System Proteins; D013925:Thromboplastin