Summary Objective To assess the relationship between the first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels and pregnancies complicated by preterm delivery. ...Materials and Methods The correlation between PAPP-A levels and gestational age at delivery was analyzed by linear regression. The probabilities of low PAPP-A multiples of the median (MoM) levels between preterm delivery and control population were analyzed by logit model. Results A positive correlation was noted between the first-trimester PAPP-A MoM levels and gestational age at delivery between 34–38 weeks ( p < 0.001). Lower PAPP-A MoM level had a significantly higher likelihood of preterm delivery ( p < 0.05). When preterm premature rupture of membranes (PPROM) and preterm labor (PTL) were analyzed separately, there was an increasing likelihood of PPROM with decreasing PAPP-A MoM levels ( p < 0.05), but not for PTL with intact membranes. Conclusion Low maternal serum PAPP-A levels during the first trimester may reflect a trophoblast invasion defect in the maternal-fetal interface, resulting in subsequent preterm delivery, particularly in those of PPROM.
Mechanism of Hypoxia-induced GCM1 Degradation Chiang, Meng-Hsiu; Liang, Feng-Yu; Chen, Chie-Pein ...
The Journal of biological chemistry,
06/2009, Letnik:
284, Številka:
26
Journal Article
Recenzirano
Odprti dostop
Preeclampsia is a major pregnancy-specific disorder affecting 5–7% of pregnancies worldwide. Although hypoxia caused by incomplete trophoblast invasion and impaired spiral arterial remodeling is ...thought to be a major cause of preeclampsia, how hypoxia affects placental development remains uncertain. GCM1 (glial cells missing homolog 1) is a transcription factor critical for placental development. In preeclampsia, GCM1 and its target genes syncytin 1 and placental growth factor, important for syncytiotrophoblast formation and placental vasculogenesis, are all decreased. Here we present evidence that GCM1 is a major target of hypoxia associated with preeclampsia. We show that hypoxia triggers GCM1 degradation by suppressing the phosphatidylinositol 3-kinase-Akt signaling pathway, leading to GSK-3β activation. Activated GSK-3β phosphorylates GCM1 on Ser322, which in turn recruits the F-box protein FBW2, leading to GCM1 ubiquitination and degradation. Importantly, the GSK-3β inhibitor LiCl prevented hypoxia-induced GCM1 degradation. Our study identifies a molecular basis for the disrupted GCM1 transcription network in preeclampsia and provides a potential avenue for therapeutic intervention.
To evaluate whether the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A) in the first trimester can predict pregnancy complicated by low birth weight (LBW) and fetal growth ...restriction (FGR).
This retrospective analysis enrolled 3,089 women with singleton pregnancy who underwent screening for Down syndrome in the first trimester of pregnancy and who delivered at Cathay General Hospital. They were divided into five groups according to the birth weight of their infants: three FGR groups of birth weight less than the 10
th, 5
th, and 3
rd centiles, a LBW group of birth weight less than 2,500 g, and a control group of all other women.
The mean multiples of median (MoM) values of PAPP-A were significantly lower in the LBW group (0.98) and the three FGR groups (< 10
th centile, 1.03; < 5
th centile, 0.96; and < 3
rd centile, 0.99) than in the control group (1.15). Women with PAPP-A less than 0.3 MoM, 0.5 MoM or in the 5
th centile (0.32 MoM) also had a significantly higher relative risk of pregnancy complicated by LBW and FGR, but the sensitivity of detection was low. The highest sensitivity using a cut-off at 0.5 MoM was 22.5%.
Our study demonstrated that a low maternal serum PAPP-A level in the first trimester is associated with pregnancy complicated by LBW and FGR, but the sensitivity was low. As a single marker, PAPP-A is not sufficient to predict LBW and FGR.
We report a case of prenatally diagnosed chromosome 7q intermediate interstitial deletion with the aid of first-trimester Down's syndrome (DS) screening. After detection of a significantly diminished ...maternal serum pregnancy-associated plasma protein A and correspondingly high DS risk, the pregnant woman underwent amniocentesis for fetal chromosomal analysis. Amniocytes revealed a 46,XY,del(7) (q21.2q31.1) karyotype and 21 weeks' sonography revealed fetal growth restriction, elevated nuchal fold thickness and cardiomegaly. After therapeutic induction at 22 weeks of gestation, a 310-gram male fetus was born with multiple gross abnormalities including hypertelorism, wide nasal bridge, low-set ears, cleft palate, prominent cheeks, prominent nuchal skin, simian crease and postaxial polydactyly. We review the associated prenatal screening findings, the sonographic profile and phenotypical features associated with chromosome 7q intermediate interstitial deletion.
To assess the sensitivity of a first-trimester combined screening test for fetal chromosomal abnormalities.
From April 1999 to December 2002, 5,036 unselected women with singleton pregnancies ...underwent a first-trimester combined test (nuchal translucency thickness, pregnancy-associated plasma protein-A, and free β-human chorionic gonadotropin) screening for Down syndrome. They included 298 (5.9%) women aged 35 years or older and 4,738 (94.1%) women aged below 35 years. A positive result was defined as an estimated Down syndrome risk of greater than 1/270.
Twenty-five (0.50%) chromosomal abnormalities were identified, with a false-positive rate of 7.1% (333/4,717) in women younger than 35 years and a false-positive rate of 17.3% (51/294) in women of advanced maternal age. The 25 chromosomal abnormalities included trisomy 21 in six fetuses, trisomy 18 and Turner's syndrome in four fetuses each, Klinefelter's syndrome, a marker chromosome and pseudohermaphroditism in one fetus each, and structural rearrangements in eight, including four with balanced translocations. One fetus with trisomy 18 was not discovered at screening, but a fetal ventricular septal defect was found on ultrasound at 30 weeks' gestation. The detection rate for fetal chromosomal abnormalities was 95.2% (20/21). If a cutoff of 1 in 200 was used, the false-positive rate would be 5.6% with the same detection rate, whereas the test still yielded a detection rate of 90.5% (19/21) with a 5% false-positive rate. In 83.3% of cases with trisomy 21 and 5.7% of normal pregnancies, fetal nuchal translucency thickness measurement was above the 95
th percentile, whereas in 0.7% of the study population and in 24% of those with fetal chromosomal abnormalities, the fetal nuchal translucency thickness was at least 3 mm.
Our results indicate that the first-trimester combined test for Down syndrome is effective in identifying fetal chromosomal abnormalities. Moreover, the measurement of fetal nuchal translucency thickness at 10 to 13 weeks of gestation enables early detection of major fetal structural anomalies.
Adenomyosis is a medical condition defined by the abnormal presence of endometrial tissue within the myometrium, in which fibrosis occurs with new collagen deposition and myofibroblast ...differentiation. In this study, the effect of several mediators and growth factors on collagen expression was investigated on human endometrial stromal cells (fibroblasts) derived from adenomyotic endometrium. Of the tested mediators, transforming growth factor beta1 (TGFbeta1) and its isoforms were effective to induce collagen and connective tissue growth factor (CTGF) expression. Collagen and CTGF induction by TGFbeta1 could be reduced by the inhibitors targeting DNA transcription, protein translation, and Smad2/3 signaling. Interestingly, TGFbeta1 induced Smad2/3 phosphorylation and CTGF mRNA expression, but not collagen mRNA expression, suggesting that TGFbeta1 mediates collagen expression through CTGF induction and Smad2/3 activation. In parallel, TGFbeta1 and CTGF also induced expression of heat shock protein (HSP) 47, a protein required for the synthesis of several types of collagens. However, only CTGF siRNA knockdown, could compromise TGFbeta1-induced collagen expression. Finally, the immunohistochemistry revealed vimentin- and alpha-SMA-positive staining for (myo)fibroblasts, TGFbeta1, collagen, and CTGF in the subepithelial stroma region of human adenomyotic endometria. We reveal here that TGFbeta1, collagen, and CTGF are expressed in the stroma of adenomyotic endometria and demonstrate that TGFbeta1 can induce collagen production in endometrium-derived fibroblasts through cellular Smad2/3-dependent signaling pathway and CTGF expression, suggesting that endometrial TGFbeta may take part in the pathogenesis of adenomyosis and ectopic endometrium may participate in uterine adenomyosis.
Background. The purpose of this study was to assess outcomes in pregnancies with a positive screen of first‐trimester combined test (nuchal translucency, pregnancy‐associated plasma protein‐A and ...free beta‐human chorionic gonadotropin).
Methods. Using a cut‐off level of 1 in 270, 216 (7.1%) women had a positive screen. Among them, 187 delivered their babies in our hospital and the adverse outcomes, such as spontaneous abortion, intrauterine fetal demize, preterm prelabor rupture of the membranes, preterm labor, intrauterine growth restriction, gestational hypertensive disorders, placenta previa, chromosomal abnormalities and fetal structural anomalies, were identified and compared with the 2097 women who screened negative for Down's syndrome.
Results. Pregnancies with a positive screen had a significantly higher risk of adverse outcomes than those with negative screens (30.5% versus 15.3%; odds ratio 2.4; p < 0.001), especially for those complicated by spontaneous abortion (odds ratio 11.4; p < 0.05) and placenta previa (odds ratio 4.3; p < 0.05).
Conclusions. Besides fetal chromosomal abnormalities and structural abnormalities, pregnancies with a positive screen for Down's syndrome in the first‐trimester had a significantly higher incidence of subsequent adverse obstetric outcomes.
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