Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome.

The syncytiotrophoblast (ST) is one of the major components of the human placenta, as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. The aim of this study was to elucidate the formation and function of the ST in trisomy 21 (Down's syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblasts were isolated from 15 trisomy 21-affected placentas (12-35 weeks gestation) and 10 gestational age-matched control placentas. In vitro cytotrophoblasts isolated from normal placenta fused to form the ST. This was associated with an increase in transcript levels and in the secretion of hCG, human placental lactogen, placental GH, and leptin. In trisomy 21-affected placentas, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of these hormones compared to those in cultured cells isolated from control age-matched placentas. These results were confirmed by a significant (P < 0.001) decrease in gene expression in total homogenates of trisomy 21-affected placentas compared to controls. These results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal development.

Correlation between selective inhibition of the cyclic nucleotide phosphodiesterases and the contractile activity in human pregnant myometrium near term.

The present study was carried out to determine the ability of various pharmacological agents to selectively inhibit each cytosolic form of phosphodiesterase isolated from the longitudinal layer of human myometria near term. Among the drugs tested, zaprinast specifically inhibits the first form of PDE which hydrolyses both substrates (cAMP and cGMP) and is stimulated by the Ca2+-calmodulin complex. A second form of PDE specific for cAMP hydrolysis and Ca2+-calmodulin insensitive is only present during pregnancy. Rolipram is the most potent and selective inhibitor of this second form. It is also the most efficient compound to inhibit in vitro the spontaneous contractions of near term myometria. The double effect of rolipram suggests an important role of the second form of PDE in the mechanisms of contractility during the pregnancy. In addition rolipram or other derivatives might be of a therapeutic interest in the prevention of prematurity in so far as they are devoid of undesirable maternal and fetal side effects.

[Doppler examination of the umbilical arteries. Its role in the surveillance of pregnancy]. / L'examen Doppler des artères ombilicales. Sa place dans la surveillance de la grossesse.

Pregnancies with a high risk of fetal growth retardation are at present watched by using clinical observations and biological parameters including ultrasound and estimation of the fetal heart rate. The Doppler waveform in the umbilical arteries provides information about circulatory resistance in the placenta. An index of resistance "R" is evaluated on the Doppler trace. The purpose of this study is to describe the score (with its possibilities and limitations) for this parameter "R" to follow-up pregnancies with fetal growth retardation and to compare it with ultrasound, biological and clinical parameters that are commonly used. Two groups of pregnancies have been explored: pregnancies with hypertension and pregnancies with idiopathic fetal growth retardation. Abnormal values of "R" correlate well with failure of fetal growth. Furthermore pathological values of "R" do not correspond to the same population as abnormal values of the other parameters. In some cases "R" is disturbed before the others are. In conclusion, this study shows that the index increases the accuracy of detection and the follow-up of chronic fetal growth retardation, particularly in cases of pregnancies with vascular placental pathology.

[Ultrasound in the study of fetoplacental circulation]. / Les ultrasons dans l'exploration de la circulation foeto-placentaire.

Exploration of fetal vessels is performed with a duplex system which combines a real-time linear imaging system 3.5 MHz and a pulsed Doppler (2.5 MHz). The transducers of the imaging and Doppler systems are associated in the same probe. Umbilical and aortic circulation have been investigated on 100 pregnancies. The umbilical artery Doppler spectrum shows an important diastolic flow which increases all along the pregnancy. A decrease of this flow occurs when the placental circulatory resistances increase. In case of severe hypertension one can note a decrease or the disappearance of the diastolic flow related to the existence of vascular placental defects (infarctus). This was observed in pathological pregnancies with hypotrophy or fetal death. The placental resistances can be quantified with the Pourcelot index R = A - D divided by A, where A is the maximum systolic amplitude and D the maximum end diastolic amplitude, both measured on the umbilical artery spectrum. Fetal blood flow measurements were performed with the same device. The mean value of the blood flow is about 170 ml/min/kg in the aorta and 120 ml/min/kg in the umbilical arteries at the end of the pregnancy. The possibility to record simultaneously fetal aorta and inferior vena cava enable us to detect abnormal heart rate such as the atrioventricular block.