Petites-filles DES : malformations utérines, fertilité, reproduction

Professeur Michel Tournaire, Réseau DES France, Forum d’Infertilité 2017

Vidéos en français: Distilbène DES : 60 vidéos à visionner sur YouTube.

Le troisième génération de victimes du médicament Distilbène® arrive aujourd’hui en âge de procréer.

Qu’en est-il au niveau de leur fertilité et risques supplémentaires en cas de grossesse ?

Le Professeur Michel Tournaire, membre du Conseil Scientifique de Réseau DES France, présente de nouveaux résultats de l’étude Distilbène 3 générations :

  • petites filles DES : malformations utérines.
  • petites filles DES : fertilité et reproduction.

Enregistrement provenant de la 4ème Journée Nationale de l’Infertilité, un forum d’information et d’aide aux personnes infertiles organisé cet automne 2017, Paris 12.

Le Distilbène DES, en savoir plus

Mécanismes épigénétique des perturbateurs endocriniens

Dr Anne Wautier, Réseau DES France, Forum d’Infertilité 2017

Vidéos en français: Distilbène DES : 60 vidéos à visionner sur YouTube.

Image credit @magicmaman_com.

Le Dr Anne Wautier, gynécologue médicale, aborde de façon très claire (et avec des exemples aidant à la compréhension) des notions complexes telles que : épigénétique, perturbateurs endocriniens, effets transgénérationnels du distilbene DES.

Enregistrement provenant de la 4ème Journée Nationale de l’Infertilité, un forum d’information et d’aide aux personnes infertiles organisé cet automne 2017, Paris 12.

Le Distilbène DES, en savoir plus

Le lait : mensonges et vérités

Les produits laitiers sont-ils nos amis pour la vie ? Vérité, mensonges et propagande

On a longtemps affirmé que le lait était bon pour la santé. Or, aujourd’hui, ses vertus sont de plus en plus remises en cause. Quelle est la différence entre le lait cru et celui que nous trouvons dans le commerce ? Les produits sans lactose ne présentent-ils que des avantages pour les consommateurs ? Le lait bio est-il réellement meilleur pour la santé ? « Xenius » mène l’enquête.

Le lait, ami ou poison ? Indispensables à une alimentation équilibrée et source de nombreux nutriments pour les uns, associés au développement de maladies pour les autres, les produits laitiers suscitent aujourd’hui une vive controverse. Enquête sur le lait et ses dérivés, sujet qui déchaîne aujourd’hui les passions.

Diffusé le 10/01/2017, arte.

Industrie agro-alimentaire : business contre santé

Les magazines de France 2, Cash Investigation, Présenté par Elise Lucet, 2016

Un film de Sandrine Rigaud avec Guillaume Coudray.

Pourquoi le jambon est-il rose ? Pourquoi a-t-il la réputation d’être bon pour les enfants ? Elise Lucet révèle les recettes inavouables des géants de l’agroalimentaire. De la Bretagne au Danemark en passant par la Californie et le Wisconsin, pendant un an, une équipe a avalé les kilomètres, en avion, en voiture et en caddy pour déterminer comment ces mastodontes de l’assiette pèsent sur les décisions de santé publique, à leur avantage. Elise Lucet prolonge l’enquête avec des experts et des responsables politiques.

Diffusé le 13/09/2016, franceinfo.

Ostéoporose, il y a comme un os

Ostéoporose : vraie menace ou fausse maladie ? – Enquête de santé, le documentaire

Dans la plupart des cas, l’ostéoporose n’est pas une maladie mais un processus naturel lié au vieillissement.

Le mode de dépistage de l’ostéoporose conduit des milliers de femmes en bonne santé à prendre des traitements préventifs dont l’efficacité est remise en cause. Des médicaments censés prévenir le risque de fracture qui peuvent avoir de graves effets secondaires. Aux Etats-Unis, ils sont au cœur de retentissants procès.

Le documentaire “Ostéoporose, il y a comme un os“, réalisé par Bruno Timsit, est suivi d’un débat animé par Michel Cymes, Marina Carrère-d’Encausse et Benoît Thevenet.

EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

BACKGROUND
Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

OBJECTIVES
Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

METHODS
We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

RESULTS
We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

CONCLUSIONS
Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.

Discussion

Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Designer Viruses Stimulate the Immune System to Fight Cancer

Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy

Swiss scientists have created artificial viruses that can be used to target cancer. These designer viruses alert the immune system and cause it to send killer cells to help fight the tumor. The results provide a basis for innovative cancer treatments.

2017 Study Abstract

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTLeff) responses. Conversely, the induction of protective tumour-specific CTLeff and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTLeff responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTLeff influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy.

Sources
  • Designer Viruses Stimulate the Immune System to Fight Cancer, University of Basel, 26 May 2017.
  • Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy, Nature Communications, doi:10.1038/ncomms15327, 26 May 2017.
  • Image : Stable transgene expression and attenuation of artLCMV in vivo, nature, Figure 2, 26 May 2017.

Environmental exposures start in the womb

Protecting Children from the Environment

Children, including adolescents, are exposed to a variety of hazards from the environments in which they live, learn and play.

Environmental exposures start in the womb, and can have effects throughout life.

Early exposure to environmental risks contributes to childhood cancers.

SOURCES

Environmental Risks and Children

Protecting Children from the Environment

A safe, healthy and protective environment is key to ensuring all children grow and develop normally and healthily. In 2015, reducing environmental risks could have prevented more than a quarter of the 5.9 million deaths of children under 5 years.

Children are particularly vulnerable to air pollution, hazardous chemicals, climate change, and inadequate water, sanitation and hygiene.

SOURCES

Protecting Children from the Environment

Protecting Children from the Environment

Children, including adolescents, are exposed to a variety of hazards from the environments in which they live, learn and play.

More than 1 in 4 child deaths could be prevented by cleaning up the environment. Each year 1.7 million deaths of children under 5 years old are linked to the environment.

Early exposure to environmental risks contributes to childhood cancers.

SOURCES