Development and hormonal functions of the human placenta.

The human placenta is characterized by the intensity of the trophoblast invasion into the uterus wall and the specificity of its hormonal functions. Placental hormones are required for the establishment and maintenance of pregnancy, adaptation of the maternal organism to pregnancy and fetal growth. In the early placenta at the maternofetal interface, the human trophoblast differentiates along two pathways: 1/ the villous trophoblast pathway including the cytotrophoblastic cells which differentiate by fusion to form the syncytiotrophoblast that covers the entire surface of the villi; 2/ the extravillous trophoblast pathway. The cytotrophoblastic cells of the anchoring villi in contact with the uterus wall proliferate and then migrate into the decidua and the myometrium but also participate to the remodeling of the spiral arteries. During the first trimester of pregnancy the spiral arteries are plugged by trophoblastic cells, allowing the development of the fetoplacental unit in low oxygen environment. At this stage of pregnancy the extravillous trophoblast secretes a large amount of hormones such as particular hyperglycosylated forms of hCG directly involved in the quality of the placentation. At 10-12 weeks of pregnancy, the trophoblastic plugs are progressively dislocated and the syncytiotrophoblast starts to bath in maternal blood. It secretes the major part of its polypeptide hormones in maternal circulation taking over the maternal metabolism in order to increase the energetic flux to the fetus. As example the placental GH (growth hormone) secreted continuously by the syncytiotrophoblast is directly involved in the insulino-resistance of pregnancy. Capturing the cholesterol from the maternal lipoproteins, the syncytiotrophoblast synthesizes also large amount of progesterone essential for the uterine quiescence. Deprived of cytochrome P450 17alpha-hydroxylase-17:20 lyase, it uses the maternal and fetal adrenal androgens to synthesize estrogens. The differentiation and hormonal functions of the human trophoblast are regulated by the environmental O2 and reflect mammalian evolution

Development and hormonal functions of the human placenta.

The human placenta is characterized by the intensity of the trophoblast invasion into the uterus wall and the specificity of its hormonal functions. Placental hormones are required for the establishment and maintenance of pregnancy, adaptation of the maternal organism to pregnancy and fetal growth. In the early placenta at the maternofetal interface, the human trophoblast differentiates along two pathways: 1/ the villous trophoblast pathway including the cytotrophoblastic cells which differentiate by fusion to form the syncytiotrophoblast that covers the entire surface of the villi; 2/ the extravillous trophoblast pathway. The cytotrophoblastic cells of the anchoring villi in contact with the uterus wall proliferate and then migrate into the decidua and the myometrium but also participate to the remodeling of the spiral arteries. During the first trimester of pregnancy the spiral arteries are plugged by trophoblastic cells, allowing the development of the fetoplacental unit in low oxygen environment. At this stage of pregnancy the extravillous trophoblast secretes a large amount of hormones such as particular hyperglycosylated forms of hCG directly involved in the quality of the placentation. At 10-12 weeks of pregnancy, the trophoblastic plugs are progressively dislocated and the syncytiotrophoblast starts to bath in maternal blood. It secretes the major part of its polypeptide hormones in maternal circulation taking over the maternal metabolism in order to increase the energetic flux to the fetus. As example the placental GH (growth hormone) secreted continuously by the syncytiotrophoblast is directly involved in the insulino-resistance of pregnancy. Capturing the cholesterol from the maternal lipoproteins, the syncytiotrophoblast synthesizes also large amount of progesterone essential for the uterine quiescence. Deprived of cytochrome P450 17alpha-hydroxylase-17:20 lyase, it uses the maternal and fetal adrenal androgens to synthesize estrogens. The differentiation and hormonal functions of the human trophoblast are regulated by the environmental O2 and reflect mammalian evolution

Biochemical characterization and modulation of LH/CG-receptor during human trophoblast differentiation.: LH/CG-R in human trophoblast differentiation.

Due to the key role of the human chorionic gonadotropin hormone (hCG) in placental development, the aim of this study was to characterize the human trophoblastic luteinizing hormone/chorionic gonadotropin receptor (LH/CG-R) and to investigate its expression using the in vitro model of human cytotrophoblast differentiation into syncytiotrophoblast. We confirmed by in situ immunochemistry and in cultured cells, that LH/CG-R is expressed in both villous cytotrophoblasts and syncytiotrophoblasts. However, LH/CG-R expression decreased during trophoblast fusion and differentiation, while the expression of hCG and hPL (specific markers of syncytiotrophoblast formation) increased. A decrease in LH/CG-R mRNA during trophoblast differentiation was observed by means of semi-quantitative RT-PCR with two sets of primers. A corresponding decrease ( approximately 60%) in LH/CG-R protein content was shown by Western-blot and immunoprecipitation experiments. The amount of the mature form of LH/CG-R, detected as a 90-kDa band specifically binding (125)I-hCG, was lower in syncytiotrophoblasts than in cytotrophoblasts. This was confirmed by Scatchard analysis of binding data on cultured cells. Maximum binding at the cell surface decreased from 3,511 to about 929 molecules/seeded cells with a kDa of 0.4-0.5 nM. Moreover, on stimulation by recombinant hCG, the syncytiotrophoblast produced less cyclic AMP than cytotrophoblasts, indicating that LH/CG-R expression is regulated during human villous trophoblast differentiation. J. Cell. Physiol. 212: 26-35, 2007. (c) 2007 Wiley-Liss, Inc

Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation.: SOD-1 and Human Trophoblast Differentiation

The syncytiotrophoblast is the major component of the human placenta, involved in feto-maternal exchanges and secretion of pregnancy-specific hormones. Multinucleated syncytiotrophoblast arises from fusion of mononuclear cytotrophoblast cells. In trisomy 21-affected placentas, we recently have shown that there is a defect in syncytiotrophoblast formation and a decrease in the production of pregnancy-specific hormones. Due to the role of oxygen free radicals in trophoblast cell differentiation, we investigated the role of the key antioxidant enzyme, copper/zinc superoxide dismutase, encoded by chromosome 21 in in vitro trophoblast differentiation. We first observed that overexpression of superoxide dismutase in normal cytotrophoblasts impaired syncytiotrophoblast formation. This was associated with a significant decrease in mRNA transcript levels and secretion of hCG and other hormonal markers of syncytiotrophoblast. We confirmed abnormal cell fusion by overexpression of green fluorescence protein-tagged superoxide dismutase in cytotrophoblasts. In addition, a significant decrease in syncytin transcript levels was observed in superoxide dismutase-transfected cells. We then examined superoxide dismutase expression and activity in isolated trophoblast cells from trisomy 21-affected placentas. Superoxide dismutase mRNA expression (P < 0.05), protein levels (P < 0.01), and activity (P < 0.05) were significantly higher in trophoblast cells isolated from trisomy 21-affected placentas than in those from normal placentas. These results suggest that superoxide dismutase overexpression may directly impair trophoblast cell differentiation and fusion, and superoxide dismutase overexpression in Down's syndrome may be responsible at least in part for the failure of syncytiotrophoblast formation observed in trisomy 21-affected placentas

Outbreak of Serogroup W135 Meningococcal Disease after the Hajj Pilgrimage, Europe, 2000

The 2000 Hajj (March 15–18) was followed by an outbreak of Neisseria meningitidis W135 2a: P1.2,5 in Europe. From March 18 to July 31, 2000, some 90 cases of meningococcal infection were reported from nine countries, mostly the United Kingdom (UK) and France; 14 cases were fatal. Although most early cases were in pilgrims, the outbreak spread to their contacts and then to those with no known pilgrim contact. In France and the UK, the outbreak case-fatality rate was compared with the rate reported from national surveillance. The risk of dying during this outbreak was higher in France and the UK, although the difference was not statistically significant. Prophylaxis for all pilgrims and their household contacts was offered in France; in the UK and other European countries, prophylaxis was recommended only for close contacts. No difference in transmission rates following intervention was detected between France and the UK

L'évolution récente de la population dans les pays de l'Arc alpin (sans l'Italie)

Zusammenfassung. — Als Alpenstaat besitzt die Schweiz 3/5 ihrer Fläche im Berggebiet. Nur etwas mehr als 1/4 der gesamten Bevôlkerung lebt in diesem Raum. Die Bevölkerungsentwicklung des Schweizer Alpen ist aufdie Verstädterungsfortschritten und den Aufschwung der niedrigen Gegenden zurtickzufiihren. Dadurch gleicht siejener der anderen Teile der Alpenkette. Neigen dieMenschen im allgemeinen in den peripheren Gebieten, sich zu konzentrieren, so капп man auch sogar im Bergareal eine Abschwächung der hôheren Lagen zugunsten der Talsohlen sowie eine starke Abnahme der mittleren Hôhen bemerken. Ziemlich wenige Städte befinden sich im Berggebiet. In einer enormen Verschiedenheit der Menschensiedlungen kann man aile Entwicklungsarten beobachten. Merkbar ist, dass die meisten homogen wachsenden Zonen den Gebieten entsprechen, wo der Fremdenverkehr vorherrscht. Zum Schluss ist es möglich festzustellen, dass die Orts-, Regional- und Landesplanungsmassnahmen die bevorstehenden Tendenzen nur kaum geändert haben.Abstract. — Switzerland has 3/5 of its territory in the mountainous region of the Alps. But only 1/4 of the population lives in this area. The demographic growth of the helvetian Alps is founded on the development of the urbanization and of the lower countries. In this way, it tends to resemble the one of other alpine regions. If the mountainous outskirts have a natural predisposition to concentrate the population, also in the mountains the higher countries decrease in favour of the valleys. There is a marked decline at the middle heights. The mountain area is not very urbanized. In a big diversity of human implantations, all kinds of evolutions cand be observed. The most of the countries with an homogeneous growth parallel to areas where the tourism has developed considerably. The measures taken for territory's adjustment have not changed the former tendencies.Résumé. — Etat alpin, la Suisse possède 3/5e de son territoire dans la zone de montagne de la chaîne, mais sur cet espace ne vit que guère plus du 1/4 de sa population. La croissance démographique des Alpes helvétiques est due avant tout aux progrès de l'urbanisation et à l'essor des parties basses. En cela, elle se rapproche de celle des autres secteurs de l'arc alpin. Si la tendance générale est à la concentration des hommes à la périphérie de la montagne, on constate dans l'aire même de cette dernière un affaiblissement des zones élevées au profit des fonds de vallée, ainsi qu 'une forte diminution aux altitudes moyennes. La zone de montagne est relativement peu urbanisée. Au sein d'une grande diversité des cellules humaines, tous les types d'évolution peuvent être observés. On remarque que la plupart des zones à croissance homogène correspondent à des régions où rayonne le tourisme. On peut enfin constater que les mesures d'aménagement du territoire et de planification n'ont pas modifié sensiblement les tendances antérieures.Billet Jean, Guibourdenche Henri. L'évolution récente de la population dans les pays de l'Arc alpin (sans l'Italie). In: Revue de géographie alpine, tome 72, n°1, 1984. pp. 5-8

PLACE DE LA PROCALCITONINE DANS LE DIAGNOSTIC DE L'INFECTION MATERNO-FOETALE (DES PHARMACIE SPECIALISEE)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Evaluation de la maturation pulmonaire foetale dans la hernie congénitale diaphragmatique (intérêt du dosage des corps lamellaires dans le liquide amniotique)

La hernie de coupole diaphragmatique (CDH) est une maladie congénitale dans laquelle les poumons des enfants atteints présentent tous à des degrés variables une hypoplasie du parenchyme pulmonaire. Le diagnostic prénatal de la CDH est relativement aisé mais sa prise en charge à la naissance reste délicate et le taux de mortalité élevé. Ceci est dû au manque de critères prénataux fiables permettant d'évaluer la maturité pulmonaire. L'étude biochimique du liquide amniotique peut se révéler utile pour apprécier la maturité pulmonaire. Son intérêt reste limité car les méthodes disponibles étaient longues, spécialisées et leurs résultats contradictoires. Des travaux récents ont montré qu'il est possible d'évaluer la maturité pulmonaire en comptant les corps lamellaires (CL) amniotiques, en raison de leurs similitudes avec les plaquettes, sur des automates d'hématologie. Notre objectif a été d'évaluer l'analyse des CL sur l'automate ADVIA 120® (Bayer, USA) et de déterminer les conditions optimales de recueil et de conservation des prélèvements. Nous avons ensuite réalisé une étude rétrospective portant sur 65 liquides amniotiques de CDH et 288 liquides témoins d'âge gestationnel apparié dans le but d'en évaluer l'intérêt dans la CDH. L'analyse des CL sur l'ADVIA 120® est facile et rapide. Elle nécessite seulement 200 L de liquide amniotique non centrifugé et non sanglant, préalablement congelé pour éliminer toute contamination par des plaquettes. Nous avons confirmé par microscopie électronique que les organites cellulaires comptés étaient bien des CL. La précision et l'exactitude de la méthode sont acceptables. Dans la population témoin, le nombre de CL augmente significativement au cours de la grossesse et particulièrement à partir de 32 SA tandis que leur volume diminue et que leur masse ne varie pas. Dans la CDH, les CL sécrétés sont morphologiquement normaux mais leur nombre est significativement diminué à partir de 32 SA. Cette diminution n'est corrélée à aucun des critères pronostiques échographiques ou radiologiques ni au devenir postnatal des nouveau-nés. Leurs valeurs prédictives restent à évaluer à une plus large échelleDespite progress in prenatal diagnosis of congenital diaphragmatic hernia (CDH), the management of affected neonates remains a major clinical concern. This is mainly due to the lack of prognosis criteria to evaluate fetal lung maturity. To do so, studies focus on sonographic and MRI findings. Biochemical assessment of fetal lung maturity appears of poor interest because it requires assays that belong to specialised laboratories and give controversial results. Amniotic fluid lamellar body (LB) count has been proposed to predict fetal lung maturity. LB represent the storage form of surfactant secreted by type II pneumocytes and can be easily analyzed in amniotic fluid using hematology analyzer. In the present study, we aimed to evaluate the interest of amniotic fluid LB analysis to predict fetal lung maturity in CDH. We made a brief evaluation of the assay, the sampling and the storage of amniotic fluid. We then conducted a retrospective study on 65 amniotic fluids from CDH affected fetuses compared to 288 amniotic fluids of age matched controls using the ADVIA 120® hematology system (Bayer, USA). Results were compared to sonographic and RMI findings and the postnatal issue. LB analysis and count is easy and rapid to perform on the ADVIA 120. It only requires 200 L of non bloody and non centrifuged amniotic fluid, previously frozen prior to analysis to eliminate platelet. We confirme that the cells count were LB using electronic microscopy. Assay accuracy and sensitivity are acceptable. In controls, we observed an increase in the LB count during the gestation and especially after > 30 WG. LB volume decreased and LB mass remained unchanged. In CDH, we observed no change in the volume and the mass of LB. However, LB count was significantly decreased only after 30 WG. This decrease was neither correlated with sonographic findings nor with the post natal evolution. In CDH, LB secreted in amniotic fluid are normal but their concentration is decreased, confirming fetal lung immaturity after 30WG. Further investigations are required to confirm their predictive valuesPARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Iodine deficiency in northern Paris area: impact on fetal thyroid mensuration.

Iodine is essential for normal fetal and neonatal development. We studied the prevalence and impact on fetal thyroid development of iodine deficiency in pregnant women in the northern part of the Paris conurbation.110 patients underwent several determinations of urinary iodine excretion (UIE) and of serum FT4, FT3, and TSH. Fetal thyroid gland size was assessed using ultrasonography.We found evidence of widespread iodine deficiency (mean UIE, 49.8 µg/L [standard deviation, 2.11]). Iodine deficiency did not correlate significantly with maternal thyroid parameters but showed a significant negative correlation with fetal thyroid gland size (rho = 0.25, P = 0.02).Iodine deficiency during pregnancy is still a problem in our geographical area and affects the fetal thyroid gland. Clinical Trials.gov NCT00162539

Anti-Müllerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection

OBJECTIVE: To evaluate anti-Müllerian hormone (AMH) as a marker of reproductive outcome after IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): Two hundred seventy-six consecutive women undergoing IVF/ICSI. INTERVENTION(S): Ovarian stimulation, oocyte retrieval, IVF, ICSI, embryo transfer, AMH, and inhibin B determinations in serum and follicular fluid (FF). MAIN OUTCOME MEASURE(S): The AMH and inhibin B concentrations in 276 matched FF/serum pairs have been determined. Different outcome groups have been compared and set in relation to the oocyte count, morphological parameters, and steroid hormone levels. RESULT(S): The concentrations of AMH and inhibin B in both serum and FF were significantly higher in the group of women who became pregnant in the corresponding treatment cycle than in those who did not conceive. Positive correlations were observed between serum inhibin B concentrations and embryo morphology (r = 0.126, 95% confidence interval 0.026-0.284). Serum and FF AMH or inhibin B correlated positively with the oocyte count and negatively with the pretreatment cycle day 3 FSH level and the total administered gonadotropin dose. CONCLUSION(S): The AMH and inhibin B levels on the day of oocyte retrieval are correlated to reproductive outcome