Survival of very premature infants is improving in France: First results of the EPIPAGE 2 study

Since 2011, nearly 7,000 premature infants have been enrolled in the EPIPAGE 2 study. This study is aimed at assessing the survival of infants born between 22 and 34 weeks’ gestation, and their subsequent outcomes. Compared with data from the EPIPAGE 1 cohort in 1997, the proportion of infants born in 2011 from the 25th week of gestation, who survived without severe neonatal disease, showed a definite increase. However, survival is still rare for infants born before 25 weeks. These results make it possible to establish the prognosis for very premature and extremely premature infants, and review the changes that have occurred in the last 15 years. They provide useful information to medical teams caring for infants and supporting families.

This study, carried out by researchers from the Inserm EPOPé team—“Obstetrical, Perinatal, and Pediatric Epidemiology Team,” at the Epidemiology and Biostatistics Sorbonne Paris Cité Research Centre (CRESS, Inserm/Paris Descartes University Unit 1153)—is published in the journal JAMA Pediatrics.



The EPIPAGE 2 study (Epidemiological Study on Low Gestational Age) is a French national study aimed at improving knowledge on the outcomes of premature infants in light of the changes that have occurred in the last 15 years. It is being conducted in 25 regions of France. From 28 March 2011 through 31 December 2011, nearly 7,000 premature infants (stillborn and live births) were enrolled in EPIPAGE 2. Information was collected from maternity and neonatal units by medical and research teams from the 25 participating regions.

The average length of a normal pregnancy is 40 weeks. An infant born before 37 weeks’ gestation (before the beginning of the 9th month of pregnancy) is considered premature, and very premature if born between 22 weeks (5 months) and 31-32 weeks (7 months).

In this study, three groups of premature infants were constituted:

– extremely premature infants (born before the end of the 6th month of pregnancy, at 22 through 26 completed weeks’ gestation)

– very premature infants (born before the end of the 7th month of pregnancy, at 27 through 31 completed weeks’ gestation)

– moderately premature infants (born at the beginning of the 8th month of pregnancy, at 32 through 34 completed weeks’ gestation)

The EPIPAGE 2 results showed that 0.44% of births took place before 27 weeks in France, 0.84% between 27 and 31 weeks, and 1.8% at 32-34 weeks.

On analysis, the 2011 data show that the more premature the infant, the lower the survival rate. Thus survival is 99% at 32-34 weeks, 94% at 27-31 weeks, 60% at 25 weeks, and less than 1% before 24 weeks.

Since premature infants are at high risk of neonatal complications, particularly affecting the brain and respiratory and digestive systems, survival rates without serious neonatal disease are lower. These are 97% at 32-24 weeks, 31% at 27-31 weeks, 30% at 25 weeks, and 12% at 24 weeks.Epipage_tableau_UK

It is from the 25th week that the researchers observe a significant improvement in the survival of premature infants in the last 15 years.

“We see a substantial increase in survival rate for infants from the EPIPAGE 2 cohort born in 2011. Compared with 1997 (the first EPIPAGE study), the proportion of infants surviving without severe morbidity has increased by 14% for infants born between the 25th and 29th weeks and by 6% for infants born between 30 and 31 weeks’ gestation,” explains Pierre-Yves Ancel, leader of the Inserm Obstetrical, Perinatal, and Pediatric Epidemiology Team behind the study. These data therefore suggest that the care of premature infants has improved in 15 years.

Results in the most immature infants, however, show little progress. They reflect great uncertainty regarding the outcome for these infants and the care that should be proposed. The results from EPIPAGE 2 could be an opportunity to reflect on the care of the smallest infants. This reappraisal should take “morbidity” and long-term sequelae into account.

“Data collected in the EPIPAGE 2 study are invaluable in defining specific care needs during childhood, and better understanding the consequences of prematurity” the researchers conclude.

Further information

Inserm EPIPAGE 2 study website:

At this time, over 4,000 children are being monitored in the study. Families have completed questionnaires at 1 and 2 years. At 2 years of age, information was also collected from the physician responsible for the medical follow-up of each child.

The next important step is follow-up at 5 years of age. This step is aimed at conducting a full review of the health and development of the children in dedicated centres.



© Inserm / Pierre Yves Ancel

Brain and spatial attention: Can the left hemisphere compensate for a lesion in the right hemisphere?

Dr Paolo Bartolomeo, Inserm Research Director and head of the PICNIC LAB[1] team at the Brain and Spinal Cord Institute (ICM, an Institute supervised by Inserm, CNRS and UPMC) and his collaborators have published the results of their research on “unilateral spatial neglect,” also known by the term “hemineglect,” in the journal Brain. People with this disorder act as if they did not know about the left side of their world. This disorder occurs primarily after an injury to the right cerebral hemisphere, for example following a stroke (cerebrovascular accident or CVA), and exacerbates the resulting disability by impeding rehabilitation and recovery. The scientists therefore searched for factors predicting the persistence of this disorder, in order to offer patients appropriate rehabilitation.

The published study shows that the two hemispheres can partially compensate for one another in the event of an injury, through incompletely understood mechanisms known as “brain plasticity.” However, results suggest that this compensation requires both hemispheres to “speak to one another” via intact connections—bundles of white matter formed by extensions of the neurons.

In the acute phase of a stroke affecting the right hemisphere, the vast majority of patients show signs of left-sided neglect (since the left side of our body is controlled by the right hemisphere and vice versa). These patients behave as if the left side of their world no longer existed. They do not eat food from the left side of their plate, they collide with furniture located on their left, and do not shave or apply make-up to the left side of the face. They also recover less well from their motor deficits than patients affected in the left hemisphere. Some of them recover with time, but spontaneous improvement of neglect is far from being the rule: at least one-third of patients showing this disorder in the acute phase continue to show signs of it over a year after acquiring their lesion. This highlights the clinical imperative to identify factors that predict the persistence of negligence, in order to offer appropriate rehabilitation to patients for whom this disorder risks becoming chronic.

Dr Paolo Bartolomeo and his collaborators monitored changes in neglect over time in 45 patients with vascular lesions in the right hemisphere. Advanced magnetic resonance imaging methods made it possible to study the condition of the fibres in the white matter that enable the different regions of the brain to communicate with one another, as well as the two hemispheres. All neglect patients had damage to the lines of communication between the anterior and posterior parts of the right hemisphere; patients with persistent neglect lasting one year after acquiring the lesion also showed damage to the posterior part of the corpus callosum, the connection that allows the two cerebral hemispheres to communicate with one another. The (healthy) left hemisphere must therefore be able to communicate with the injured (right) hemisphere, in order to learn to compensate for the visuospatial defects provoked by the brain lesion. Patients with damage to the corpus callosum are at risk of developing chronic neglect, and should therefore have priority access to rehabilitation treatments.

PhotoCP web

A patient with spatial neglect fails to copy the elements located on the left side of a picture. © PICNIC LAB – ICM

[1] Physiological Investigations of Clinically Normal and Impaired Cognition

Influenza: France crosses epidemic threshold

According to the weekly bulletin of the Sentinelles network, the incidence of influenza crossed the epidemic threshold last week, with 231 cases detected in general practice per 100,000 inhabitants. A figure that exceeds the epidemic threshold (179 cases per 100,000 inhabitants).

At regional level, the highest rates of incidence were found in: Limousin, Auvergne and Corsica.

According to researchers, the epidemic of influenza-like illness is set to increase in intensity this week, thus confirming the onset of the epidemic.

The study presently has 5,416 participants registered on the website. This research project, established by the Sentinelles network (Inserm – UPMC) and the French Institute for Public Health Surveillance, enables everyone to participate in influenza surveillance and research in metropolitan France, anonymously, voluntarily and directly online.

Additional data on influenza-like illness measured in the general population and the Sentinelles network’s Bulletin of 21/01/15 are available at

carte grippe 22012015

Elucidating the origin of MDR tuberculosis strains

A study has focused on the evolutionary history of the mycobacterium that causes tuberculosis, and more specifically on the Beijing lineage associated with the spread of multidrug resistant forms of the disease in Eurasia. While confirming the East-Asian origin of this lineage, the results also indicate that this bacterial population has experienced notable variations coinciding with key events in human  history. They also demonstrate that two multidrug resistant (MDR) clones of this lineage started to spread concomitantly with the collapse of the public health system in the former Soviet Union, thus highlighting the need to sustain efforts to control tuberculosis. Finally, this work has made it possible to identify new potential targets for the treatment and diagnosis of this disease. This study was carried out by scientists at the Centre d’Infection et d’Immunité de Lille (CNRS/Institut Pasteur de Lille/Inserm/Université de Lille) and the Institut de Systématique, Evolution, Biodiversité (CNRS/Muséum national d’Histoire naturelle/UPMC/EPHE), working in collaboration with a large international consortium[1]. Its findings were published on 19 January in Nature Genetics.
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Tuberculosis bacilli visualized through scanning electron microscopy © Jean-Pierre Tissier (INRA, Villeneuve d’Ascq) et Franco Menozzi (Institut Pasteur de Lille)

Tuberculosis remains a major public health problem. The disease is  responsible for nearly one million-anda-half deaths each year, and strains of the infective agent that are increasingly resistant to antibiotics continue to emerge. The lineage of so-called Beijing strains is closely associated in particular with the spread of multi- and ultra-resistant tuberculosis in Eurasia. By studying the genetic fingerprints[2] of almost 5,000 isolates from this lineage, originating from 99 countries (i.e. the largest collection analyzed to date[3]), and then analyzing around a hundred bacterial genomes in more detail, the authors of this study were able to identify its original source and track the main stages in its spread.

The results of these genetic analyses indicate that the Beijing lineage emerged nearly 7,000 years ago in a region lying between northeastern China, Korea and Japan, whence it radiated throughout the world in successive waves associated with historical movements of human populations from east to west. In the modern era, the bacterial population first saw its size increase during the industrial revolution and the First World War. These phases of growth were probably linked to increases in human population density and deprivation respectively associated with these events. The only phase of  decline observed thereafter was concomitant with the widespread use of antibiotics during the 1960s. This decline ended in the late 1980s, and was  related to the HIV/AIDS epidemic and the onset of multidrug resistance.

This study has also shown that the more recent epidemic spread of the two  strains most closely associated with MDR in Central Asia and Eastern Europe coincided with the collapse of the public health system in the former Soviet Union. These findings underline the importance of maintaining highly  efficient disease control systems and developing new and more effective methods for  diagnosis and treatment.

In this context, the scientists identified a series of mutations and genes that might be connected with epidemic episodes and multidrug resistance. These genes constitute potential targets for treatment and for the development of new and more rapid diagnostic methods for multidrug resistance, based on  genomic sequencing.

[1] Consortium also led by the Borstel Research Center (Germany).
[2] Based on an internationally standardized molecular method, these analyses were performed by the team at the Centre d’Infection et d’Immunité de Lille, working in collaboration with the company Genoscreen.
[3] This collection was built up thanks to an international consortium, which includes the US Center for Disease Control.

A new MOOC invites the general public to discover a stem cell culture laboratory

University of Nantes, Inserm and Thinkovery have joined forces to produce a new kind of MOOC (Massive Open Online Course). Alternating as it does between theory and practice, “Ouvrez les portes du laboratoire: cellules et cellules souches,” (Open the laboratory doors: cells and stem cells) invites members of the public to discover, by means of enriched video content, the actual work done by researchers at Université de Nantes, Inserm and CNRS.

From 16 March 2015, all Internet users will thus be able to understand how and why researchers grow stem cells in the laboratory, and will be able to attend a course on cell biology.

PhotoCP web

Institut du thorax UMR 915 – Inserm/Latron, Patrice

After more than a year of design and production, the MOOC “Ouvrez les portes du laboratoire: cellules et cellules souches” will begin on 16 March 2015, and will be accessible on the FUN (France Université Numérique/France Digital University) platform. Registration is already open.

To put this novel MOOC together, teams from Université de Nantes, in partnership with Inserm, have joined forces with a new medium devoted to research, Thinkovery.

They have combined their knowledge and ability to produce this six-week online course, and over fifty two- to five-minute videos, mainly with financial support from the Pays de la Loire Region and L’Oréal Research and Innovation. L’Oréal also contributed to preparing the content of this MOOC that covers aspects of somatic hair follicle stem cells.

“We regularly open up our research laboratory to the public, but for one thing it is difficult for us to accommodate everyone, and for another thing, such days do not give the public the opportunity to follow a project from start to finish.

It was this observation that gave us the idea. Based on the same principle as the MOOCs that throw open the doors of lecture theatres, we wanted to throw open the doors of our laboratory via the Internet,” says Patricia Lemarchand, a physician, lecturer and researcher at the Institut du Thorax at Nantes, of the initiative for the project with Loïc Le Gac of the Thinkovery company.

The MOOC alternates between two series:

The “Côté Cours” (Lecture Side) introductory videos on cell biology describe the main concepts needed to understand the “Côté Laboratoire” (Laboratory Side) videos, which immerse the visitor in the daily work of a joint research team.

To register for the MOOC

The MOOC will begin on 16 March 2015

Registration is open! Go to the FUN platform to register for free for the

MOOC “Ouvrez les portes du laboratoire: cellules et cellules souches:”

Stem cell therapy for heart failure: first implant of cardiac cells derived from human embryonic stem cells

On the 21 October 2014, Professor Philippe Menasché and his team from the cardiovascular surgery service of the Georges Pompidou European Hospital, AP-HP, carried out a transplant of cardiac cells derived from human embryonic stem cells*, according to a method developed by the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital, directed by Professor Jérôme Larghero and through research led by this group within Inserm. The surgery, coupled with a coronary bypass*, was carried out on a woman of 68 years suffering from severe heart failure. Ten weeks after the intervention, the patient is feeling well, her condition has improved markedly, with no complications having been observed. This promising advance was presented this Friday, 16 January 2015 at the XXV European Days Conference of the French Society of Cardiology.

Human embryonic stem cells. Transplantation of undifferentiated human embryonic stem cells into rat heart organotypic cultures. Presence of human cells, in the cardiac parenchyma of the rat two months after injection. The human cells are positive for human nuclear antigen marking (red). Cardiac rat tissue is positive for cardiac troponin 1 marking (green). I-Stem (Institiute for Stem Cell Therapy), Evry Genopole. Inserm/Habeler, Walter

The transplant was carried out as part of a clinical trial developed by the Public Hospitals of Paris (AP-HP) and through the work of the teams from AP-HP, Inserm and the universities of Paris-Descartes and Paris-Diderot. The cardiac cells were prepared according to a technique developed by the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital. The cytogenetics laboratory of the Antoine Béclère Hospital and the French General Agency for Health Products and Equipment also contributed to the preparation of this phase I trial which will enable the verification of the safety and feasibility of the procedure

For 20 years Professor Menasché, currently co-director of an Inserm team within PARCC (Paris Centre for Cardiovascular Research), and his colleagues have been involved in stem cell* therapy for heart failure.

The team first tested the implant of skeletal muscle stem cells in necrosed areas of the heart in the laboratory. These cells were implanted into the heart of a patient with heart failure for the first time in the world on 15 June 2000. Following an initial series of these implants, always coupled with a coronary bypass, the team coordinated a European multi-centre, randomised, placebo-controlled trial whose results have still not been able to establish any significant benefit of these cells on the contractile function of patients’ hearts.
One of the conclusions drawn from this trial was that to be fully efficient, transplanted cells should resemble the cells of the tissue to be repaired as much as possible, in this instance cardiac tissue. It was then decided to venture along the path of embryonic stem cells.  Derived from embryos conceived in in vitro fertilisation, these cells do in fact possess pluripotent properties, that is, they are capable of developing into any type of cell of the body, including of course cardiac cells, as soon as they receive the appropriate signals during the culture cycle in the laboratory.

In 2007, the team then composed of, among others, Michel Pucéat, Director of Research at Inserm, and Philippe Menasché showed that human embryonic stem cells could be differentiated into cardiac cells after being transplanted into the failing hearts of rats.
Since then, many experiments have been carried out on different animal species in order to validate the efficacity of these cells and to optimise conditions which can guarantee maximum safety. At the end of this stage, a bank of pluripotent embryonic stem cells was formed in the conditions which satisfied all regulatory constraints applying to biological products for human use. Then, the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital, still in liaison with the Inserm teams, developed and tested “specialisation” procedures for cells in order to produce “young” cardiac cells from them.
The focus was then on the purification of the cells directed like so in order to ensure that the final product was expunged of any remaining pluripotent cells which could be potentially tumorigenic.

Besides, as initial experience with muscular stem cells showed the limitations of administering cells by multiple injections, their transfer is now performed using a patch that the cells are incorporated into. This patch is then placed on the area of the infarction. To that end, after the purification stage, the cardiac cells are incorporated into a circular fibrin gel which is applied, during the surgical procedure, to the necrosed area with just a few sutures ensuring that it is anchored to the cardiac tissue.

“This type of surgery is aimed at serious heart failure which doesn’t respond to the usual medicinal treatments but is not at the stage of a complete heart transplant. This is a promising advance, which we hope will enrich the therapeutic arsenal available to treat heart failure today” explains Prof. Menasché. “We are continuing the trial, which authorises us to carry out four other transplants. It would seem already that the benefits of the cells are linked mainly to the substances that they secrete.  The direct administration of the substances, without going through a transplant of productive cells, is a path to explore”.

This project has been entirely financed by funds from public intstitutions and societies and was authorised by the French National Agency for the Safety of Medicines and Health Products (ANSM) after agreement with the Agency for Biomedicine for the importation and research on human embryonic cells.


Cell therapy: refers to cell transplants aiming to restore the function of tissue or an organ when it has been altered by an accident, illness or ageing. These therapies have benefited from recent scientific advances on stem cells and give millions of patients the hope of regenerative medicine.

Embryonic or pluripotent stem cells: they can renew indefinitely (self-renewal), multiply in a culture and be differentiated into more than 200 types of cell. In the course of development, they are destined to form all types of the body’s tissue.

Coronary bypass: a technique that enables the redirection of the bloodstream towards the cardiac muscle, by using a graft (coming from the saphenous vein or from a thoracic artery….) One end of the graft is connected to the aorta, the main artery supplying the coronary arteries; the other end is connected to the coronary artery, situated just behind the site of the obstruction. This creates a detour enabling the oxygenated blood to circulate towards the heart.

Inserm is launching a development programme for a new generation vaccine strategy against the Ebola virus

A clinical trial project, coordinated by Inserm, involving the testing of a preventive vaccine against Ebola has been selected by the European Commission. The protocol plans to include participants throughout Europe and Africa to evaluate immune response and tolerance to a vaccine strategy named “prime boost”, based on the use of two candidate vaccines developed by Janssen, a pharmaceutical company of Johnson & Johnson.

Microscopic view of the ebola virus

© Fotolia

The development and rapid access to treatment and candidate vaccines are among the WHO’s recommendations to stop the transmission of the Ebola virus and prevent the international spread of infection. Since the beginning of the epidemic, the French and international scientific community has been actively working towards these objectives.

Inserm has established an academic partnership with the London School of Hygiene and Tropical Medicine (LSHTM), as well as an industrial partnership (Crucell Holland BV; one of Janssen’s companies), The University of Oxford and the Centre Muraz to develop a vaccination from Phase 1 to Phase 3 that combines two vaccines derived from viral vectors (Ad26.ZEBOV et MVA-BN-Filo[1]). This project has been selected for funding by the European Commission under the second call for IMI2 (Innovative Medicines Initiative) projects. As part of this programme, Inserm will conduct Phase 2 trials in Europe and Africa, coordinated by Prof. Rodolphe Thiébaut.

These Phase 2 trials will evaluate the tolerance and quality of the immune response to the vaccine strategy. These tests will supplement data from Phase 1 trials that are currently in progress in the United States, England and are soon to be conducted in Africa. The data will be available in March 2015 and will be critical to evaluating effectiveness in areas at risk.

“This strategy, unlike conventional immunization protocols that involve one or more administrations of the same vaccine, is based on the concept of a vaccination involving several steps with two different vectors that will expose the organism to the same antigens in several ways. This is a new approach in the development of a vaccine against Ebola” stated Prof. Yves Levy, Inserm CEO.

The Grant Agreement is currently being finalised. Definitive information on the project, including the budget, will be published once the agreement has been signed.

[1] Both viral vectors used are conventional vectors that are already widely used in humans in several vaccines for other infectious diseases.

The biological basis of good health

In a biological sense, what does it mean to be “in good health”? This far-reaching question is the focus of the “Laboratoire d’Excellence” project Milieu Intérieur (“Environment Within”), coordinated at the Institut Pasteur by Professor Matthew Albert (Dendritic Cell Immunobiology Unit, Institut Pasteur/Inserm) and Dr. Lluis Quintana-Murci (Human Evolutionary Genetics Unit, Institut Pasteur/CNRS). The Milieu Intérieur cohort is the first French cohort of its kind, comprised of a thousand healthy donors. Studying this cohort will help define the parameters of a healthy immune system. The recent analysis of the initial results generated from the cohort represents an important milestone for the scientists in this consortium. In addition to having direct applications in the field of health, the results of this program are of direct interest to the scientific community, as they define a new control system for patient population studies. It should also improve our understanding of the variability between individuals, thereby providing reference tools for adapting treatments with a view to developing a personalized approach to patient care.

Despite the fact that immune responses are extremely complex and vary from one person to another, medical practices and public health policies are based on a single model of patient care and drug development. The Milieu Intérieur project was created specifically to address this paradox. This Laboratoire d’Excellence project involves more than thirty scientists from the top French research centers[1]. At the Institut Pasteur the project is coordinated by Professor Matthew Albert (Inserm research director) and Dr. Lluis Quintana-Murci (CNRS research director). Its primary objective is to define and increase understanding of the notion of a “healthy” donor, in order to give the research world an unprecedented opportunity to study the relationship between genetics, immunity and environment.

The scientists have just published the recruitment criteria for a cohort of healthy donors, comprising 500 French men and 500 French women aged between 20 and 69 and all in good health. The project has already led to the constitution of a biobank of different samples, including blood, nasal and stool samples as well as skin biopsies. The scientists have also collected medical, nutritional and sociodemographic data, as well as information about donors’ lifestyles.

The statistical approach initially adopted by the scientists enabled them to pinpoint the known correlation between certain biological profiles and the age and sex of donors. It confirmed in particular that LDL cholesterol levels increase with age and that creatinine – which measures renal function – is higher in men than in women. These initial results highlighted the integrity and significance of the data collected, and validated the Milieu Intérieur cohort as a benchmark group for the French population.

With the help of biological and epidemiological data, the scientists were also able to observe the impact of environmental and lifestyle factors on the immune system. For example they observed an increase in white cells circulating in the blood stream and a reduction in certain classes of antibodies (IgG.) that could identify smokers amongst the donors of the cohort. This work highlights a more general impact of tobacco on health, which goes beyond pulmonary toxicity. This and other environmental and lifestyle factors will be placed in the wider context once all additional phenotypic data have been analyzed.

In the long term, the Milieu Intérieur project aims to provide a new reference framework and data control system for patient studies. By providing a better understanding of the variability of immune responses between individuals, it should also constitute a first step towards personalized medicine, tailoring treatment to the individual and developing drugs and diagnostic tests that match the genetic and immune profile of each patient.

[1] Institut Pasteur, Institut Curie, Paris-Diderot University, Paris-13 University, INSERM and CNRS

Bisphenol A: Alternative products that may also be harmful

Bisphenol F and bisphenol S, which are used as substitutes for bisphenol A in certain applications, have the same negative effect on human foetal testes as bisphenol A. This has recently been shown by René Habert and his colleagues at the Joint Research Unit 967 “Stem Cells, Radiation and Genetic Instability” (CEA/Inserm/Paris Diderot University)[1] using the same in vitro method that allowed the team to analyse the negative effect of bisphenol A on the testis in 2012[2].

These results are online at the Fertility and Sterility journal website.

The manufacture and sale of babies’ feeding bottles containing bisphenol A have been banned in Europe since January 2011. In addition, the manufacture, export, import and marketing of all food packaging containing bisphenol A is banned in France from January 2015. Alternative products, bisphenol S and bisphenol F, are currently being studied or are already in use. Even though their chemical structure is similar to bisphenol A, the safety of these products has never been tested in humans and other mammals and no regulations currently exist concerning this.

Culture de testicules foetaux humains

R. Habert/Inserm

To assess the harmful effects of endocrine disruptors[3] on the testis development during foetal life, Réné Habert and his colleagues at the Laboratory of Development of the Gonads (UMR 967 – “Stem Cells, Radiation and Genetic Instability” – CEA/Inserm/Paris Diderot University) have been using an original experiment system for several years, which they have developed and named the Fetal Testis Assay (FeTA)[4]. This method allows foetal testes to be kept in a petri dish for several days to assess the effects of the addition of different chemicals on their development and function. Thanks to this method, the researchers provided the first experimental proof that bisphenol A inhibits the production of testosterone in the human foetus. A concentration equal to 2 micrograms per litre of bisphenol A in the culture medium was sufficient to produce these effects This concentration is equal to the average concentration generally found in the blood, urine and amniotic fluid of the population.

Researchers have used the same culture system in this new study, the results of which were published in the Fertility and Sterility journal. They observed that the exposure of human foetal testes to bisphenol S or bisphenol F reduces the production of testosterone that is identical to the reduction caused by bisphenol A. It is the first time bisphenol S and F have been shown to have a harmful effect on physiologic function in humans.


Bisphenol A is a chemical compound that is included in the composition of plastics and resins. It is notably used in the manufacture of food containers and is also found in the protective films used inside food and beverage cans. Several studies have shown that this component has harmful effects on reproduction, metabolism and the brain. The full impact of bisphenol A occurs during foetal life.

Testosterone produced by the testes in humans and mammals during foetal life is necessary for the masculinisation of internal and external genitalia. Without this hormone, these organs can spontaneously develop in a female sense. A decrease in foetal testosterone production can lead to defects in masculinisation observed at birth (such as hypospadias and cryptorchidism). Furthermore, it is likely that a lack of testosterone produced during foetal life can result in a reduced sperm count in adulthood.

Researchers have also compared the response to bisphenol S and F in human foetal testes to those in the foetal testes of rats and mice. They have observed that humans are far more sensitive to bisphenol S and F than mice.


[1] CEA-IRCM (Institute of Molecular and Cellular Radiobiology), Fontenay-aux-Roses CEA centre.

[2] Press release 17.01.2013 – L’effet néfaste du bisphénol A prouvé expérimentalement (Harmful Effects of Bisphenol A Proven Experimentally) (Plos One, December 2012)

[3] A substance or mixture not produced by the body that alters the function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or sub-populations.

[4] In collaboration with the Antoine-Béclère Hospital in Clamart.

Suicide rate and increased unemployment

A study conducted by Inserm’s Centre for Epidemiology on Medical Causes of Death (CépiDc) and the Paris public hospital system (AP-HP) highlights an association between suicide rate and unemployment in metropolitan France between 2000 and 2010.

The statistical model actually reveals a mean 1.5% increase in suicide rate, both sexes combined, for a 10% increase in unemployment rate. This association is clearer in men aged 25-49 years, for whom the rise in unemployment has been accompanied by a 2.6% increase in suicide rate.

Published last Tuesday in Bulletin Épidémiologique Hebdomadaire (BEH), a weekly epidemiological bulletin published by InVS (French Institute for Public Health Surveillance), this work is based on suicide mortality data compiled by CépiDc in France between 2000 and 2010. The latter were cross-correlated with the corresponding unemployment rates for the quarter and region.

The researchers, however, make it clear that no cause and effect relationship can be deduced from these results, and recall the importance of individual circumstances (environmental factors, psychiatric profiles of individuals, etc.).