Biomedical subjects

V Sapin

Publications and source records attributed to V Sapin.

At least 19 recordsLinked to original sources

PubMed2007

Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study.

OBJECTIVES: To describe the true incidence, prenatal detection rate and fetal outcome of congenital diaphragmatic hernia (CDH) in a systematically registered population over an 18-year period and to determine any change in trends over time. METHODS: This was a retrospective study of all cases of CDH registered in the Central-Eastern France Birth Defects Registry from 1986 to 2003. All fetuses and infants up to 1 year of age diagnosed with CDH were registered, including miscarriages later than 22 weeks of gestation, stillbirths and terminations of pregnancy (TOP). Routine prenatal screening consisted of three ultrasound examinations and there was no upper limit of gestational age for TOP. RESULTS: Five hundred and one cases of CDH were identified from a total of 1 835 022 live births (2.7 cases per 10 000 live births). The overall prenatal detection rate was 54%. There was a significant increase over time in the detection rate mainly for associated CDH and left-sided CDH (P < 0.0001), and in the proportion of neonates delivered in tertiary centers (P < 0.0001). The overall survival rate at discharge was 47% and this increased significantly over time for isolated CDH (P = 0.04), whereas it was lower and remained stable for associated CDH (P = 0.64). The TOP rate for isolated CDH did not vary significantly in contrast to that for associated CDH cases in which the TOP rate increased over time, progressively replacing the neonatal death rate (P = 0.01). CONCLUSIONS: Over an 18-year period, this large population-based study demonstrated increasing prenatal detection rates for associated CDH and left-sided CDH and confirmed an increasing survival rate mainly for isolated CDH.

Female↗

PubMed2006

Two-dimensional gel electrophoresis based technologies for potential biomarkers identification in amniotic fluid: a simple model.

To assess the efficiency of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and of two-dimensional electrophoresis and ammoniacal silver staining (2D-E), different amounts of soybean trypsin inhibitor and horse myoglobin were added to amniotic fluid. In this model, a minimum of 5 to 10 ng of "artificial" biomarkers was detected.

Amniotic Fluid↗

PubMed2005

[Neonatal morbidity after conservative management followed by systematic delivery at thirty-four weeks of gestation in preterm rupture of membranes].

OBJECTIVE: To evaluate the neonatal morbidity and its risks factors in case of uncomplicated preterm rupture of membranes managed conservatively with subsequent planned delivery at 34 weeks of gestation. PATIENTS AND METHODS: We studied retrospectively 42 consecutive neonates systematically delivered at 34 weeks of gestation after more than 48 hours of conservative management for uncomplicated preterm rupture of membranes. Conservative management was conducted in a single tertiary care center and consisted in corticotherapy and in antibiotherapy (amoxycilline during 7 days). We evaluated the neonatal mortality rate, the incidence of infection, respiratory distress, neurological disorders, and we looked for their prenatal risks factors. RESULTS: Forty-two neonates were included. The median gestational age at rupture was 31.1 weeks of gestation (from 25 to 33.9 weeks). The median duration of expectant management was 20 days (from 2.4 to 65 days). We observed 7 cases of neonatal infection but no septic failure, 18 cases of respiratory distresses among which 9 required a tracheal intubation for a mean duration of 3.7 days, no perinatal encephalopathy (5 cases of subependymal haemorrhage) and no neonatal death. We isolated one single risk factor that was the lowest gestational age at rupture in case of subsequent respiratory distress (29.6 vs 31.9 weeks; P=0.02). DISCUSSION AND CONCLUSION: Neonatal morbidity in this population consisted mainly in respiratory distresses with an increased incidence when gestational age at rupture decreased.

Female↗

PubMed2004

[Obstetrical prognosis of labour induction with mifepristone after 41 weeks of gestation].

OBJECTIVE: To compare the mode of delivery in two groups of patients selected by their response after induction of labour with mifepristone. PATIENTS AND METHODS: We studied retrospectively 89 cases of labour induction with viable children after 41 weeks of gestation. Bishop scores were less than 6. Patients were given 200 mg of mifepristone per day for 48 h. They were retrospectively divided into group 1 (spontaneous onset of labour or premature rupture of membranes before the third day) and group 2 (not in labour by that date). RESULTS: The mean Bishop score at inclusion was 3.1 +/- 1.3. Among the 51 patients (53.9%) in group 1, one required prostaglandins and we performed 10 cesarean sections. In group 2, the mean Bishop score at the 3rd day was 4.4 +/- 1.3 (P < 0.0001). Twenty-four patients required prostaglandins (P < 0.0001) and we performed 17 cesarean sections (P = 0.01). The number of cesarean sections increased with the dose of prostaglandins (P = 0.025). We observed no maternal or fetal complications. DISCUSSION AND CONCLUSIONS: Mifepristone was successful in inducing labour spontaneously in over 50% of pregnancies after 41 weeks of gestation. In the other group, the probability of vaginal delivery was reduced especially when high doses of prostaglandins were required. After the use of mifepristone, we suggest to shorten the duration of prostaglandin administration (two applications of 2 mg dinoprostone) before performing cesarean section.

Adult↗

PubMed2004

Transcriptional control of the human pregnancy-specific glycoprotein 5 gene is dependent on two GT-boxes recognized by the ubiquitous specificity protein 1 (Sp1) transcription factor.

Pregnancy-specific glycoprotein 5 gene (PSG-5) belongs to the human pregnancy-specific glycoprotein family, encoded by eleven highly similar and transcriptionally active genes. High levels of PSG biosynthesis are restricted to the placenta syncytiotrophoblast and are essential for the maintenance of normal gestation in mammalian species. We have investigated here the nature of the transcription factors that recognize the FP1 (-455/-433) and the CPE (-147/-140) regulatory sequences that significantly contribute to basal PSG-5 promoter activity. Both elements bear a similar GT-box motif; and DNA-protein complex formation, as well as promoter activity, is largely dependent on the integrity of these GT-box sequences. Gel shift, super gel shift and UV-crosslinking experiments clearly demonstrate that the ubiquitous specificity protein 1 (Sp1) is the major transcription factor involved in complex formation with both cis-acting elements in normal term placenta tissue and in PSG-non-expressing COS-7 cells. Furthermore, transfection experiments indicate that Sp1 activates PSG-5 promoter constructs. In addition, we show that Sp1 is indeed co-expressed with PSG genes in the syncytiotrophoblast cells, stressing its potential role in the in vivo regulation of PSG expression.

Animals↗

PubMed2003

[Recurrence of multiple chorio-angiomas: a case-report].

Diffuse chorioangiomatosis is a rare placental pathology characterized by multiple chorioangiomas, inducing a high risk of fetal complications, especially cardiovascular, with a risk of fetal death. The physiopathology is not clearly established but seems to be related with an over-expression of vascular growth factors related to hypobaric-hypoxia. Here, we describe a case of recurrent chorioangiomatosis with fetal demise. No risk factors were identified (high altitude, genetic disease like Beckwith-Wiedemann, diabetes). Intra-amniotic, plasmatic values of alphafetoprotein and plasmatic beta gonadotrophin chorionic hormone remained low. Ultrasonographic assessment of placental thickness was in the normal range, at 22 and 32 weeks of gestation. In case of previous chorioangiomatosis, we recommend a weekly sonographic monitoring to diagnose fetal complications associated with an early inpatient hospitalization for daily surveillance at the age of previous accidents. Labor will be induced in case of fetal intolerance or systematically after 37-38 weeks of gestation.

Adult↗

PubMed2001

Co-localization of KLF6 and KLF4 with pregnancy-specific glycoproteins during human placenta development.

Pregnancy-specific glycoproteins (PSGs) are major placental proteins essential for the maintenance of normal gestation. However, little is known about their gene expression regulation during placentation. It was previously demonstrated that the human core promoter binding protein recently renamed Krüppel-like factor (KLF) 6 binds to a highly conserved sequence within the PSG promoters and is mainly expressed in human term placenta. Here, we determined the expression pattern of the 13 other KLFs during human placental development. We demonstrate that eight KLFs exhibit specific expression patterns in human placental tissues and membranes, in favor of a functional cooperation of specific KLFs during placentation. In addition, we demonstrate that KLF6, KLF4 and PSG proteins are co-expressed in same cell types of placental villi and membranes. This experimental evidence further strengthens the potential cross talk of both transcription factors for PSG gene regulation in vivo.

DNA-Binding Proteins↗

PubMed2001

Retinol mobilization from cultured rat hepatic stellate cells does not require retinol binding protein synthesis and secretion.

Retinol mobilization from retinyl esters stores of hepatic stellate cells (HSCs) is a key step in the regulation of mammalian retinol homeostasis, but the precise mechanisms of such a mobilization are still poorly understood. Using primary cultures of HSCs, we first demonstrated that HSCs expressed immunoreactivity against retinol-binding-protein (RBP) when cultured in a medium containing RBP but were unable to synthesize RBP transcripts and proteins. Using pulse and chase-type experiments, we demonstrated that radioactive retinol was released in culture medium without binding proteins. Inhibition of protein secretion by brefeldin A did not modify quantitatively retinol release. This data ruled out, for the first time, the direct involvement of RBP in retinol mobilization from HSCs. Moreover, HSCs co-cultured with primary isolated hepatocytes displayed an increase of retinol transfer from HSCs to hepatocytes when they established direct physical contacts, as compared with co-cultures without contact. Based on this latter data, a mechanism of retinol mobilization from HSCs via the hepatocytes using retinol transfer through cellular membranes is proposed.

Animals↗

PubMed2001

Use of transgenic mice model for understanding the placentation: towards clinical applications in human obstetrical pathologies?

The mammalian embryo and fetus are unable to develop without a well-established, functional placenta. This transitory yet indispensable structure attaches the conceptus to the uterus and establishes the vascular connections necessary for nutrient and gaseous exchange between maternal and fetal compartments. Genetic targeting strategy allows the generation of mice lacking a specific gene. Such approaches reveal: (i) the high incidence of mutant embryonic or fetal death in utero, and (ii) the extraembryonic (placental) causes of these deaths. Due to the similarities presented between mouse and human placenta, we propose to use the potential of mouse targeting experiments as a model in order to understand human obstetrical pathologies. In this paper, we first review genes that have been demonstrated to be required in mice for implantation, choriovitelline and chorioallantoic placentation. Using examples (integrins, homeoboxs, hepatocyte growth factor or epidermal growth factor receptor...) we demonstrate the reality and efficiency of such an approach. Other candidate genes (receptor of leukemia inhibitory factor, Wnt2 or retinoic acid receptor alpha...) in order to understand, prevent and treat human obstetrical pathologies.

Animals↗

PubMed2000

Differential expression of retinoic acid-inducible (Stra) genes during mouse placentation.

Several retinoid binding proteins and nuclear receptors are specifically expressed in murine placenta. However, little is known about molecular events and target genes regulated by retinoids during placentation. Here, we report that several retinoic acid-inducible (Stra) genes, originally isolated by a differential screening procedure, exhibit specific expression patterns in mouse placental tissues. Three Stra genes, including the ephrinB1 receptor tyrosine kinase ligand, are prominently expressed in the regions of exchanges between maternal and embryonic circulations, i.e. the yolk sac and/or the labyrinthine zone of the mature placenta. The Meis2 homeobox gene appears to be specifically expressed in maternally-derived cell populations. Three other Stra genes, including the AP-2-related gene AP-2gamma, are differentially expressed in the trophoblastic cell lineage. Thus, retinoids may regulate various signaling pathways in specific placental cell-types.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Spatio-temporal distribution of cellular retinoid binding protein gene transcripts in the developing and the adult cochlea. Morphological and functional consequences in CRABP- and CRBPI-null mutant mice.

The expression patterns of the mouse cellular retinoid binding protein genes were investigated by in situ hybridization analysis in the inner ear from 10.5 days post coïtum (dpc) up to the adult stage. The cellular retinoic acid binding protein II (CRABPII) and cellular retinol binding protein I (CRBPI) were present in a widespread and abundant pattern in cochlear structures during embryogenesis. Expression of the cellular retinoic acid binding protein I (CRABPI) is restricted during development in Kölliker's organ whilst cellular retinol binding protein II (CRBPII) is only visible after birth with a ubiquitous distribution in most regions of the cochlea including nervous components. No CRABP or CRBP transcripts were observed in the auditory receptors. Morphological observations of CRBPI- and CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural modification at the level of the organ of Corti. Furthermore, electrophysiological tests performed by measuring distorsion-product otoacoustic emissions and auditory brainstem evoked responses did not present significant alteration of the auditory function for the different types of mutants. The expression of retinoid binding proteins in cochlear structures during embryogenesis could suggest important roles for these proteins during ontogenesis and morphogenesis of the inner ear. Despite these observations, morphological and functional data from mutant mice did not present obvious modifications of the cochlear structures and auditory thresholds. It is therefore unlikely that CRABPs and CRBPI are directly involved in development of the cochlea and hair cell differentiation.

Age Factors↗

PubMed2000

Effect of vitamin A status at the end of term pregnancy on the saturation of retinol binding protein with retinol.

BACKGROUND: Vitamin A (retinol), which is required for normal fetal development and successful gestation, circulates in the blood bound to a specific protein, the retinol binding protein (RBP). Little is known about the transport and metabolism of this complex protein or about retinol status during normal human pregnancy. OBJECTIVE: The aim of this study was to assess retinol status and transport modalities of retinol in well-nourished women with normal pregnancies, a population poorly investigated compared with pathologic and malnourished pregnant women. DESIGN: The maternal blood and cord blood concentrations of retinol, vitamin E, beta-carotene, RBP, and transthyretin of pregnant French women at term (n = 27) were measured and compared with values from a nonpregnant control group (n = 27). In addition, holo-RBP (retinol bound), apo-RBP (retinol free), and total protein were assessed in both groups to enable the hemodilution occurring during pregnancy to be taken into consideration and to evaluate the extent of saturation of RBP with retinol. RESULTS: Healthy pregnant women at term had normal serum circulatory amounts of retinol, vitamin E, binding proteins, and beta-carotene. However, they had less binding of retinol to RBP (holo-RBP: 49.9% in pregnant women, 54.0% in cord blood, and 77.5% in the control group). CONCLUSION: The results of this study suggest that retinol homeostasis and transport are modified during normal human pregnancy.

Adult↗

PubMed2000

Esterification of vitamin A by the human placenta involves villous mesenchymal fibroblasts.

Vitamin A (retinol) and its active derivatives (retinoic acids) are essential for growth and development of the mammalian fetus. Maternally derived retinol must pass the placenta to reach the developing fetus. Despite its apparent importance, little is known concerning placental transfer and metabolism of retinol, and particularly of placental production and storage of retinyl esters. To elucidate this metabolic pathway, we incubated, in the presence of retinol, 1) human full-term placental explants and 2) primary cultures of major cells types contributing to placental function: trophoblasts and villous mesenchymal fibroblasts. We used HPLC to determine the types and concentrations of retinyl esters produced by these explants and cells. About 14% of total cellular retinol in placental explants was esterified. The most abundant esters were myristate and palmitate. Primary cell cultures showed that fibroblasts efficiently produced retinyl esters, but trophoblasts did not. In both types of experiments, no retinyl esters were detected in the culture medium, suggesting that retinyl esters were produced for storage purpose. These results suggest that villous mesenchymal fibroblasts are primary sites of retinol esterification and storage in the placenta.

Adult↗

PubMed1999

Cellular retinol-binding protein I is essential for vitamin A homeostasis.

The gene encoding cellular retinol (ROL, vitA)-binding protein type I (CRBPI) has been inactivated. Mutant mice fed a vitA-enriched diet are healthy and fertile. They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensable for RA synthesis. However, CRBPI deficiency results in an approximately 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells. This reduction is due to a decreased synthesis and a 6-fold faster turnover, which are not related to changes in the levels of RE metabolizing enzymes, but probably reflect an impaired delivery of ROL to lecithin:retinol acyltransferase. CRBPI-null mice fed a vitA-deficient diet for 5 months fully exhaust their RE stores. Thus, CRBPI is indispensable for efficient RE synthesis and storage, and its absence results in a waste of ROL that is asymptomatic in vitA-sufficient animals, but leads to a severe syndrome of vitA deficiency in animals fed a vitA-deficient diet.

Animals↗

PubMed1999

The Krüppel-like core promoter binding protein gene is primarily expressed in placenta during mouse development.

The human core promoter binding protein (hCPBP) has been identified as a DNA-binding protein involved in the regulation of TATA box-less genes like those encoding the pregnancy-specific glycoproteins. Structurally, hCPBP contains three zinc fingers in the C-terminal domain, which is highly conserved in a number of proteins that constitute the Krüppel-like family of transcription factors. In the present work, we report the molecular cloning of the mouse CPBP (mCPBP) and its expression pattern during development as well as in adult tissues. The mouse cDNA encodes a protein of 283 amino acids that share 94.4% of identity with the hCPBP. The highest level of mCPBP transcript was detected in placenta, and its expression was lower in total embryos and in adult tissues. We also show by in situ hybridization that during embryonic development the mCPBP gene is mainly expressed in extra-embryonic structures throughout gestation; essentially no specific expression was detected in embryonic tissues. Our data demonstrate that CPBP transcript is enriched in the trophoblastic tissue and strongly suggest that its encoded polypeptide regulates target genes involved in placental development and pregnancy maintenance.

Amino Acid Sequence↗

PubMed1998

Spatial distributions of retinoic acid receptor gene transcripts in the prenatal mouse inner ear.

The expression patterns of the three mouse retinoic acid (RA) receptor gene isotypes (RARalpha, RARbeta, and RARgamma) and retinoid X receptor gene isotypes (RXRalpha, RXRbeta, and RXRgamma) have been investigated by in situ hybridization analysis of their RNA transcripts in the inner ear of mouse fetuses at 18.5 days of gestation. Two RARs (RARalpha and RARgamma) and two RXRs (RXRalpha and RXRbeta) presented an almost ubiquitous transcript distribution with overlapping expression in several regions of the cochlea, such as Kölliker's organ, the organ of Corti, the spiral limbus, and nervous structures. The organ of Corti showed an enhanced in situ labeling with RARalpha and RXRbeta. By contrast, RARbeta and RXRgamma displayed more restricted expression patterns. RXRgamma in particular was strongly expressed in Kölliker's organ and in the spiral ganglion. This expression pattern suggests that RA may be involved in the differentiation of several cochlear cell types. Moreover, the colocalization of several RAR and RXR gene transcripts suggests possible heterodimerization between these receptors in several regions of the cochlea.

Animals↗

PubMed1998

Differential expression of the TEF family of transcription factors in the murine placenta and during differentiation of primary human trophoblasts in vitro.

We describe the molecular cloning of murine (m) Transcriptional Enhancer Factor (TEF)-5 belonging to the TEF family of transcription factors. We show that mTEF-5 is specifically expressed in trophoblast giant cells and other extra-embryonic structures at early stages of development. At later stages, mTEF-5 is specifically expressed in the labyrinthine region of the placenta and in several embryonic tissues. We further show that the other mTEFs are differentially expressed in extraembryonic structures and in the mature placenta. Interestingly, human (h)TEF-5 is specifically expressed in the differentiated syncytiotrophoblast of the human term placenta and its expression is upregulated during the differentiation of cytotrophoblasts to syncytiotrophoblast in vitro, whereas that of hTEF-1 is down-regulated. Together with previous results describing hTEF-binding sites in the human placental lactogen-B gene enhancer, these novel observations support a role for hTEF-5 in the regulation of this gene. We further propose that the hTEF factors may play a more general role in placental gene regulation and development.

Amino Acid Sequence↗

PubMed1997

Defects of the chorioallantoic placenta in mouse RXRalpha null fetuses.

The active derivatives of vitamin A (the retinoids) play important and multiple roles in mammalian development and homeostasis. We have previously shown that specific retinoic acid receptors are expressed in the chorioallantoic placenta of the mouse and that among these, RXRalpha is strongly expressed in the developing labyrinthine zone (Sapin, V., Ward, S. J., Bronner, S., Chambon, P., Dollé, P., Dev. Dyn. 208, 199-210, 1997). Here, we show that mouse fetuses with a targeted disruption of the RXRalpha gene develop defects of the chorioallantoic placenta. Both morphological abnormalities and alterations in the expression of molecular markers were found, mostly confined to the labyrinthine zone of placentas from mid-late gestation mutants. This region exhibited edema, abnormal stasis of maternal blood, and signs of disruption of the endothelial layer of fetal vessels. We also detected a reduction in the number of lipid droplets in the trophoblastic layer and abnormal fibrin deposits in the junctional zone of the mutant placentas. These abnormalities most probably result in an impairment of the functional capacities of exchange between the maternal and fetal circulations in the mutant placentas. Thus, placental defects could represent an extraembryonic cause of lethality for RXRalpha null mutant fetuses, in addition to the previously described embryonic cardiac defects.

Allantois↗