Alexandra Benachi

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (237)706.97 Total impact

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    ABSTRACT: We identified three doublesex and mab-3-related transcription factors (DMRT) that were sexually differentially expressed in human fetal gonads and present in the ovaries at the time of meiotic initiation. These were also identified in murine embryonic female germ cells. Among these, we focused on DMRTA2 (DMRT5), whose function is unknown in the developing gonads, and clarified its role in human female fetal germ cells, using an original xenograft model. Early human fetal ovaries (8 to 11 weeks post- fertilization) were grafted into nude mice. Grafted ovaries developed normally, with no apparent overt changes, when compared to ungrafted ovaries at equivalent developmental stages. Appropriate germ cell density, mitotic /meiotic transition, markers of meiotic progression and follicle formation were evident. Four weeks after grafting, mice were treated with siRNA, specifically targeting human DMRTA2 mRNA. DMRTA2 inhibition triggered an increase in undifferentiated FUT4-positive germ cells and a decrease in the percentage of meiotic γH2AX-positive germ cells, when compared with mice that were injected with control siRNA. Interestingly, the expression of markers associated with pre-meiotic germ cell differentiation was also impaired, as was the expression of DMRTB1 (DMRT6) and DMRTC2 (DMRT7). This study reveals, for the first time, the requirement of DMRTA2 for normal human female embryonic germ cell development. DMRTA2 appears to be necessary for proper differentiation of oogonia, prior to entry into meiosis, in the human species. Additionally, we developed a new model of organ xenografting, coupled with RNA interference, which provides a useful tool for genetic investigations of human germline development.
    Molecular Human Reproduction 07/2014; · 4.54 Impact Factor
  • Journal de gynecologie, obstetrique et biologie de la reproduction. 07/2014;
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    Cell reports. 05/2014; 7(4):933-4.
  • PLoS ONE 04/2014; · 3.53 Impact Factor
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    ABSTRACT: Abstract Objective: To describe a new grading method for stomach position(SP) in fetuses with left-sided congenital diaphragmatic hernia(L-CDH) using ultrasound and to correlate SP to liver position and to liver-to-thoracic cavity volume ratio(LiTR) using magnetic resonance imaging. Methods: SP were graded at the level of the 4-chamber view as following: grade 1-to-4 respectively for stomach not visualised, visualised anteriorly at the apex of the heart, stomach showing abdominal structures anteriorly and stomach with its larger part posterior to the level of the atrial-ventricular heart valves. The LiTR was calculated and correlated to SP using the Mann-Whitney U-test. Results: Seventy-four fetuses were included. Median LiTR for grade 1 SP was 0% and was not different from median LiTR for grade 2 SP(0%, p=NS). Median LiTR for grade 3 SP was 14.9% and was significantly higher than for grade 2 SP(p<0.001). Similarly, median LiTR for grade 4 SP was 20.7% and was significantly higher than for grade 2 SP(p<0.05). When SP was grade 1 or 2, liver was intra-abdominal in 21(84%) out of 25 fetuses while it was always intrathoracic for SP 3 or 4. Conclusion: In L-CDH, SP as described represents a simple indirect measurement of intrathoracic position and quantification of liver.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 03/2014; · 1.36 Impact Factor
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    ABSTRACT: To describe precisely prenatal ultrasound features in congenital cytomegalovirus (CMV) infection. We retrospectively evaluated the ultrasound descriptions of cases of congenital CMV infection between 2004 and 2013. In 69 congenital CMV infections, related ultrasound abnormalities were reported in 30 cases (43.5%). There were both extracerebral and cerebral abnormalities in 16 cases, purely abnormal brain features in 10, and purely extracerebral features in 2. 19/30 cases presented extracerebral features of 11 different sorts of abnormalities, mainly hyperechogenic bowel (10 cases) and intrauterine growth retardation (9 cases). 24/30 cases presented cerebral features of 13 different sorts, mainly brain calcifications (12 cases) and occipital horn cavity (11 cases). The main ultrasound findings in our series are not specific to CMV infection. However, a frequent finding attracted our attention: the anechogenic cavity located on the extremity of the occipital horn, a region which contains numerous proliferating and differentiating germinal cells. By improving knowledge of ultrasound findings linked to CMV infection, ultrasound sensitivity may be improved. Understanding why CMV leads to lesions of the occipital horn may help clarify the pathophysiology of congenital infection. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 02/2014; · 2.68 Impact Factor
  • Alexandra Benachi, Jean-Marc Costa
    Journal de Gynécologie Obstétrique et Biologie de la Reproduction 02/2014; · 0.45 Impact Factor
  • Mikaël Tassin, Alexandra Benachi
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    ABSTRACT: To review prognostic parameters reported recently in the evaluation of abdominal wall defects in the first trimester. Evaluation of abdominal wall defects in the first trimester is based principally on associated structural or chromosomal anomalies. In the case of gastroschisis, which is rarely associated with other anomalies, evaluation of prenatal or postnatal outcome is based mainly on the course of pregnancy. In the case of isolated omphalocele in the first trimester, recent studies have evaluated parameters that could help predict prenatal or postnatal outcome. We review recent studies using new parameters to diagnose abdominal wall defects in the first trimester and to provide early prenatal counselling to parents regarding prenatal and postnatal prognosis.
    Current opinion in obstetrics & gynecology 02/2014; · 2.49 Impact Factor
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    ABSTRACT: Fetal testis is a major target of endocrine disruptors (EDs). During the last twenty years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human Fetal Testis Assay (r/m/hFeTA). With this approach, we compared the effects of 6 potential EDs [(mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin] and one signalling molecule [retinoic acid (RA)] on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in human and rodent for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the 3 species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses the qualitative response is species-specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.
    Reproduction 02/2014; · 3.56 Impact Factor
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    ABSTRACT: Interstitial duplication within the long arm of chromosome 20 is an uncommon chromosome structural abnormality. We report here the clinical and molecular characterization associated with pure 20q13.2 duplication in three unrelated patients. The most frequent clinical features were developmental delay, facial dysmorphism, cardiac malformation and skeletal anomalies. All DNA gains occurred de novo, ranging from 1.1 Mb to 11.5 Mb. Compared with previously reported conventional cytogenetic analyses, oligonucleotides array CGH allowed us to refine breakpoints and determine the genes of interest in the region. Involvement of SALL4 in cardiac malformations and NFATC2 gene disruption in both cardiac and skeletal anomalies are discussed.
    European journal of medical genetics 01/2014; · 1.57 Impact Factor
  • Alexandra Benachi, Jean-Marc Costa
    Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 01/2014;
  • Alexandra Benachi, Sabine Sarnacki
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    ABSTRACT: With the development of prenatal ultrasound and of foetal medicine, the paediatric surgeon has extended his knowledge of the natural history of surgical malformations. He is a part of the prenatal team and parents should always be referred to him when a surgical malformation is suspected, even when termination of pregnancy is planned because of an expected poor prognosis. Direct contact between the prenatal medicine specialist and the paediatric surgeon is also highly recommended to ensure continuity in the messages delivered to the parents. Postnatal counselling does not compare with prenatal counselling and the paediatric surgeon has learned from the obstetrician to modulate his talk by including other conditions that might affect the outcome of the foetus, especially genetically determined syndromes. When the foetal malformation is diagnosed very early, especially in the first trimester, it therefore seems important for the consultation with the paediatric surgeon to be scheduled when the complementary exams required by the anomalies diagnosed are done, in order to avoid later contradictory messages. Repeated consultations should be favoured as they allow provision of more precise information regarding changes in ultrasound and/or MRI images and so decrease parents’ anxiety and help them to take their decision. Foetal surgery, which has reached various stages of development in different countries, requires paediatric surgeons and obstetricians to join forces to optimize procedures and evaluate their benefit/risk ratio. Since 2004, the National Rare Disease Plan in France has allowed the creation of Rare Disease Centres, which deal with congenital malformations and produce recommendations for the healthcare pathway of these patients by means of a multidisciplinary approach. This greatly enhances interdisciplinary communication and ensures that best care is provided to the parents to be and to their child.
    Seminars in Pediatric Surgery. 01/2014;
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    ABSTRACT: To evaluate the accuracy of ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of placenta accreta and to define the most relevant specific ultrasound and MRI features that may predict placental invasion. This study was approved by the institutional review board of the French College of Obstetricians and Gynecologists. We retrospectively reviewed the medical records of all patients referred for suspected placenta accreta to two university hospitals from 01/2001 to 05/2012. Our study population included 42 pregnant women who had been investigated by both ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for each case by 2 raters in order to score features that predict abnormal placental invasion. Sensitivity in the diagnosis of placenta accreta was 100% with ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity on ultrasonography were intraplacental lacunae and loss of the normal retroplacental clear space. Increased vascularization in the uterine serosa-bladder wall interface and vascularization perpendicular to the uterine wall had the best positive predictive value (92%). At MRI, uterine bulging had the best positive predictive value (85%) and its combination with the presence of dark intraplacental bands on T2-weighted images improved the predictive value to 90%. Ultrasound imaging is the mainstay of screening for placenta accreta. MRI appears to be complementary to ultrasonography, especially when there are few ultrasound signs.
    PLoS ONE 01/2014; 9(4):e94866. · 3.53 Impact Factor
  • Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 01/2014;
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    ABSTRACT: Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12 mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE®) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up.
    Journal of Clinical Virology. 01/2014;
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    ABSTRACT: Polymicrogyria (PMG) is a clinically heterogeneous malformation of cortical development, characterized by a loss of the normal gyral pattern that is replaced by many small and infolded gyri separated by shallow sulci that are partly fused in their depths. Causes of PMG are heterogeneous and include acquired and genetic causes. There are more than 100 syndromes possibly associated with PMG but mutations in specific genes such as SRPX2, GPR56, TUBB2B, TUBB3, NHEJ1, TUBA1A, TUBA8, and WDR62 have been reported only in a minority of patients.
    Neurogenetics 09/2013; · 3.58 Impact Factor
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    ABSTRACT: Vitamin D insufficiency is characterized, since 2005, by 25(OH)D concentration less than 75nmol/L (or 30ng/mL). Vitamin D could interfere with many mechanisms involved in preeclampsia's pathogenesis including trophoblastic invasion and immunomodulation as well as blood pressure control and proteinuria. Occurrence of preeclampsia and gestational diabetes seems to be linked to vitamin D deficiency but recent data in the literature are contradictory. Vitamin D supplementation during pregnancy is controversial. Some societies consider it unnecessary and others recommend up to 2000UI/d. There is no reported case of teratogenicity linked with vitamin D intake.
    La Presse Médicale 09/2013; · 0.87 Impact Factor
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    ABSTRACT: Type I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB. Immunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5). FGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls. These findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.
    Orphanet Journal of Rare Diseases 09/2013; 8(1):130. · 4.32 Impact Factor
  • Archives de Pédiatrie 09/2013; 20S1:S1-S4. · 0.36 Impact Factor
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    ABSTRACT: Congenital cystic adenomatoid malformations (CCAM) of the lung are the most frequent congenital lung malformations. Their diagnosis is based on histological features. CCAM consist of bronchopulmonary cystic lesions which are classified according to the presence and cysts size. Type I CCAM are composed of large cysts (>2cm) lined by a columnar pseudostratified epithelium. Type II CCAM contain multiple small cystic lesions (<1cm) lined by a flattened cuboidal epithelium. Type III CCAM are more solid and contain immature structures resembling the pseudoglandular stage of lung development. Ultrasonography (US) allows early detection during the second trimester of pregnancy as cystic, and/or hyperechoic fetal lung lesions. Although most CCAM remain asymptomatic, CCAM can cause polyhydramnios or fetal hydrops, respiratory distress at birth, infections and pneumothoraces during infancy, and may give rise to malignancies. Serial US allow detection of complications, and planification of delivery. Complicated forms require an urgent treatment. In fetuses with a macrocystic life-threatening lesion, a thoraco-amniotic shunt can be placed. Microcystic compressive forms may respond to prenatal steroids. Post-natal symptomatic lesions require early surgery. The treatment of asymptomatic forms remains controversial. Some recommend a non-operative approach with a long-term clinical and radiological following, whereas other favour a preventive surgical excision. The origin of CCAM remains unknown. Recent advances suggest a transient and focal abnormality in lung development which may result from an airway obstruction. This article reviews the diagnosis, treatment, and pathophysiology of CCAM.
    Revue de Pneumologie Clinique 07/2013; · 0.20 Impact Factor

Publication Stats

2k Citations
706.97 Total Impact Points


  • 2010–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Université Paris-Sud 11
      • Faculty of Medicine
      Orsay, Île-de-France, France
  • 2013
    • Hôpital Foch
      Lutetia Parisorum, Île-de-France, France
  • 2011–2013
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
    • University-Hospital Brugmann UVC
      Bruxelles, Brussels Capital Region, Belgium
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France
  • 2007–2013
    • Université René Descartes - Paris 5
      • • Faculté de Médecine
      • • Faculté de Médecine
      Paris, Ile-de-France, France
  • 2012
    • University of Burgundy
      Dijon, Bourgogne, France
  • 2010–2012
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2007–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008–2011
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
    • Hôpital de Poissy Saint Germain en Laye
      Saint-Germain, Île-de-France, France
  • 2005–2010
    • French Institute of Health and Medical Research
      • Institut Mondor de Recherche Biomédicale (IMRB) U955
      Paris, Ile-de-France, France
  • 2005–2009
    • Université Paris Descartes
      • Faculté de Médecine
      Lutetia Parisorum, Île-de-France, France
  • 2006–2008
    • Universitair Ziekenhuis Leuven
      • Department of Gynaecology and obstetrics
      Leuven, VLG, Belgium
  • 2005–2008
    • College of Obstetrics and Gynecology of Leon
      Aquitaine, France
  • 2006–2007
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      • Faculty of medicine
      Créteil, Île-de-France, France
  • 2002–2007
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2005–2006
    • Hadassah Medical Center
      • Department of Obstetrics and Gynaecology
      Jerusalem, Jerusalem District, Israel