RESUMO
OBJECTIVE: To evaluate the alteration in epidermal growth factor-like domain 7 (EGFL7) mRNA expression in maternal blood from pregnancies affected by early-onset intrauterine growth restriction (IUGR) at 20-24 weeks. METHOD: Case-control study encompassing six women with pregnancies affected by IUGR (cases) matched in a 1 : 7 ratio for gestational age and fetal gender with 42 controls. We quantified EGFL7 mRNA expression in normal and IUGR patients. Matched rank-sum analysis and multiples of median were used to evaluate differences of the marker of interest between cases and controls. Spearman regression analysis was used to correlate the estimated fetal weight at blood sampling with the EGFL7 mRNA values. RESULTS: The mean observed rank in the IUGR group was significantly higher than that of controls (6.67 vs 4.19, p = 0.01). Pregnancies affected with IUGR exhibited 1.70-fold higher levels of maternal EGFL7 mRNA compared with matched controls (p = 0.014). EGFL7 mRNA values were inversely correlated with estimated fetal weight (Spearman's ρ = -0.429, p = 0.198). CONCLUSION: Early IUGR at 20-24 weeks' gestation is associated with higher values of EGFL7 expression in maternal plasma.
Assuntos
Fatores de Crescimento Endotelial/sangue , Retardo do Crescimento Fetal/sangue , Adulto , Proteínas de Ligação ao Cálcio , Estudos de Casos e Controles , Família de Proteínas EGF , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Segundo Trimestre da Gravidez/sangue , RNA Mensageiro/sangueRESUMO
OBJECTIVE: To retrospectively investigate whether the genetic profile from chorionic villous sampling (CVS) found in euploid fetuses with increased NT differs from matched controls. STUDY DESIGN: We employed cDNA microarray technology to characterize and compare the gene expression profile of chorionic villous tissues (which encompass the trophoblast and inner mesenchymal core) belonging to four singleton male fetuses with increased NT at 10-11 weeks' gestation. A pool of four normal chorionic villous tissues belonging to four respective fetuses, matched for gestational age and gender, was used as controls. RESULTS: In euploid fetuses, we found several underexpressed genes, possibly involved in mechanisms associated with the abnormal NT thickness. All these genes are likely to belong to the mesenchymal core of the villus that originates from the extraembryonic mesoderm, and thus might be closely representative of the embryonic genetic profile. They include: (1) genes of embryonic development and differentiation such as Endothelin 3 (EDN3) and secreted frizzled-related protein 4 (SFRP4); (2) genes of the extracellular matrix (ECM) metabolism such as tissue inhibitor of metalloproteinase1 (TIMP1), and disintegrin-like and matrix metalloproteinase (MMP) (reprolysin type) with thrombospondin type 1 Motif or ADAMTS2, exostoses (multiple)-like 1 (EXTL1), heparan sulfate (HS) 6-O-sulfotransferase 1 or HS6ST1, fibronectin 1 (FN1) and Integrin Alpha 10 (ITGA10) involved in HS and proteoglycan bio-synthesis, ECM synthesis and cell-matrix adhesion; (3) genes involved in vessel formation and differentiation such as angiogenic factor (VG5Q), and in blood pressure control and muscle contraction, like Endothelin 3 or EDN3 and sarcolemma associated protein (SLMAP). Such lower expressions of the villous tissues might be related to an immature genetic profile of the embryo development as well as abnormal regulation of ECM bio-synthesis and/or improper vessel growth and blood pressure control. Also, the results partially support the theories proposed for NT enlargement such as altered composition of ECM and abnormal/delayed development of the circulatory system. CONCLUSIONS: Abnormal extraembryonic genetic expression is found at 10-11 weeks' gestation in euploid fetuses with increased NT. If both extra- and intraembryonic mesoderms express the same genetic alterations, then microarray analyses on CVS could be used to screen several mesoderm-derivate anomalies.