RESUMEN
OBJECTIVE: Besides foetal or maternal disorders, placental dysfunction is a major cause of intrauterine growth restriction (IUGR). Although numerous macro- and histopathological changes have been described, little is known about the precise aetiology and the contribution of foetal/placental genes in this disorder. DESIGN: Placental tissues of 20 IUGR and control neonates were analysed by microarray technique. Four of the regulated genes with possible relevance in the pathogenesis of IUGR and its consequences were further studied in placentas of 27 IUGR and 35 control newborns. RESULTS: Elevated gene expression of leptin, corticotrophin-releasing hormone (CRH), and IGF-binding protein-1 (IGFBP-1) in IUGR placentas could be confirmed in the larger group by real-time PCR, whereas prolactin showed no significant difference. Accordingly, protein expression of leptin and IGFBP-1 depicted by Western blot was elevated in IUGR, prolactin was not different. Birthweight standard deviation score (SDS) correlated negatively to leptin, IGFBP-1, and CRH, whereas placental weight correlated only to IGFBP-1. Leptin correlated negatively to gestational age of IUGR patients and positively to placental score, a marker of severity of impaired foeto-placental circulation. CONCLUSIONS: As confirmed in a large group of IUGR and control samples, the up-regulated factors leptin, IGFBP-1, and CRH may serve as candidate genes for the prediction of subsequent metabolic consequences in IUGR newborns. These three factors may not only influence growth of the foetus, but might also interact with programming of its metabolic functions, which has to be determined in an ongoing study.
Asunto(s)
Retardo del Crecimiento Fetal/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Placenta/metabolismo , Adulto , Western Blotting , Femenino , Retardo del Crecimiento Fetal/genética , Humanos , Recién Nacido , Leptina/metabolismo , Masculino , Embarazo , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
OBJECTIVE: The human placenta as part of the feto-placental unit may influence fetal endocrine systems and may therefore represent a very important link between intrauterine growth restriction (IUGR) and metabolic disorders in later life. We aimed to analyze the effect of sample origin on gene expression of placental factors potentially involved in fetal programming in IUGR versus appropriate for gestational age growth (AGA) to standardize sample collection procedure for a multicenter approach. DESIGN: Placental gene expression of insulin-like growth factor-binding protein (IGFBP)-1, prolactin, corticotropin releasing hormone (CRH) and leptin was measured and compared between proximal, intermediate and peripheral region of the placenta in 22 IUGR (proven by anomalous placental Doppler velocimetry) and 19 AGA neonates. RESULTS: Whereas no difference in gene expression was seen in the proximal portion, in the intermediate placental region mRNA expression of IGFBP-1 (p = 0.01), prolactin (p = 0.04), CRH (p = 0.01) and leptin (p = 0.04) was increased in IUGR samples compared to controls. At the placental periphery, gene expression of these placental transcripts showed a higher expression level in IUGR placentas without statistical significance, except for leptin (p = 0.03). CONCLUSION: Placental sampling site seems to be relevant for detecting differences in gene expression between IUGR and AGA neonates.
Asunto(s)
Hormona Liberadora de Corticotropina/biosíntesis , Retardo del Crecimiento Fetal/genética , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/biosíntesis , Leptina/biosíntesis , Placenta/fisiopatología , Prolactina/biosíntesis , Adulto , Hormona Liberadora de Corticotropina/genética , Femenino , Retardo del Crecimiento Fetal/metabolismo , Humanos , Recién Nacido , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Leptina/genética , Masculino , Placenta/metabolismo , Embarazo , Prolactina/genética , Estudios Prospectivos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
In male patients with congenital anomalies of the kidney and urinary tract, an increased incidence of a polymorphism in the angiotensin type 2 receptor gene (AT2R) has been identified. The AT2R has been shown to be involved in apoptosis, particularly during embryogenesis. The aim of this study was to examine the A-->1675G transition polymorphism in intron 1 of the AT2R gene that is located on the X chromosome in patients with coarctation of the aorta (CoA) with and without Ullrich-Turner syndrome (UTS). Screening of DNA samples was performed with restriction fragment length polymorphism analysis. Ninety-seven patients with CoA, 28 girls with UTS, 10 girls with UTS and CoA, and 96 control individuals were studied. There was no significant difference in the distribution of A and G-genotypes in any of the patient groups compared to controls. An A-->1675G transition in the AT2R gene seems not to be involved in the pathogenesis of aortic coarctation.