Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions. Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period), either n-3 PUFA-free diet (CTL), or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction. As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response

Impact of exposure to diesel exhaust during pregnancy on mammary gland development and milk composition in the rabbit

Exposure to fine-particulate air pollution is a major global health concern because it is associated with reduced birth weight and an increased risk of cardiovascular disease. Here we have investigated the potential for exposure to diesel exhaust during pregnancy to influence mammary gland development and milk composition. Female rabbits were therefore exposed by nose-only inhalation to either diluted diesel exhaust fumes (1 mg/m3) or clean air for 2h/day, 5 days/week, from the 3rd to the 27th days of pregnancy. On Day 28 of pregnancy, mammary glands were collected from twelve females (six controls and six diesel-exposed) and assessed for morphological and functional alterations. Milk samples were collected from eighteen dams (nine controls and nine diesel-exposed) during early (days 2 to 4) and established (days 13 to 16) lactation to verify the composition of fatty acids and major proteins and leptin levels. The mammary alveolar lumina contained numerous fat globules, and stearoyl CoA reductase expression was higher in mammary epithelia from diesel exhaust-exposed rabbits, which together suggested increased mammary lipid biosynthesis. Gas chromatography analysis of the composition of milk fatty acids revealed a sharp rise in the total fatty acid content, mainly due to monounsaturated fatty acids. Liquid chromatography-mass spectrometry analysis of milk samples enabled identification and quantification of the main rabbit milk proteins and their main phosphorylated isoforms, and revealed important changes to individual casein and whey protein contents and to their most phosphorylated isoforms during early lactation. Taken together, these findings suggest that repeated daily exposure to diesel exhaust fumes during pregnancy at urban pollution levels can influence lipid metabolism in the mammary gland and the lipid and protein composition of milk. As milk may contribute to metabolic programming, such alterations affecting milk composition should be taken into account from a public health perspective

A perspective on the developmental toxicity of inhaled nanoparticles.

This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo–fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis

Environnement et grossesse : ce que nous apprennent les modèles animaux

International audienc

Nutrition et origines développementales des maladies

Nutrition et origines développementales des maladie

Effects of Exposure to Diesel Exhaust During Pregnancy : lessons from a Rabbit Model

International audienc

Diet before and during pregnancy and offspring health: The importance of animal models and what can be learned from them

This review article outlines epidemiologic studies that support the hypothesis that maternal environment (including early nutrition) plays a seminal role in determining the offspring's long-term health and metabolism, known as the concept of Developmental Origins of Health and Diseases (DOHaD). In this context, current concerns are particularly focused on the increased incidence of obesity and diabetes, particularly in youth and women of child-bearing age. We summarize key similarities, differences and limitations of various animal models used to study fetal programming, with a particular focus on placentation, which is critical for translating animal findings to humans. This review will assist researchers and their scientific audience in recognizing the pros and cons of various rodent and non-rodent animal models used to understand mechanisms involved in fetal programming. Knowledge gained will lead to improved translation of proposed interventional therapies before they can be implemented in humans. Although rodents are essential for fundamental exploration of biological processes, other species such as rabbits and other domestic animals offer more tissue-specific physiological (rabbit placenta) or physical (ovine maternal and lamb birth weight) resemblances to humans. We highlight the important maternal, placental, and fetal/neonatal characteristics that contribute to developmentally programmed diseases, specifically in offspring that were affected in utero by undernutrition, overnutrition or maternal diabetes. Selected interventions aimed at prevention are summarized with a specific focus on the 1000 days initiative in humans, and maternal exercise or modification of the n-3/n-6 polyunsaturated fatty acid (PUFA) balance in the diet, which are currently being successfully tested in animal models to correct or reduce adverse prenatal programming. Animal models are essential to understand mechanisms involved in fetal programming and in order to propose interventional therapies before they can be implemented in humans. Non-rodent animals are particularly important and should not be neglected, as they are often more physiologically-appropriate models to mimic the human situation

Diabète et obésité maternelle et paternelle: quelles conséquences pour la descendance?

un abstract sera disponibleDiabète et obésité maternelle et paternelle: quelles conséquences pour la descendance? . Club de Recherches Cliniques du Québec (CRCQ) 201

Origines développementales de la santé et des maladies : quelle signification pour la fertilité

International audienceD’après le concept des origines développementales de la santé et des maladies (DOHaD), il existe une relation entre l’environnement nutritionnel maternel, le développement fœtoplacentaire et le risque pour la descendance de développer des maladies à l’âge adulte. Ce concept a été validé à la fois chez l’homme et les animaux de rente. Au cours de la gestation, le placenta, dont l’origine est fœtale, est l’organe responsable des échanges entre la mère et le fœtus. Il est sensible à un environnement maternel délétère, lequel peut affecter sa morphologie, ses flux sanguins, les échanges fœto-maternels (transporteurs) et/ou sa fonction endocrine, et ainsi altérer, globalement, son efficacité. Parmi, les environnements maternels délétères, figure la malnutrition, laquelle regroupe la sous-nutrition, la restriction protéique, la surnutrition, les carences en micronutriments, les contaminants alimentaires, etc. Le placenta peut s’adapter à un tel environnement pour assurer la survie du fœtus ; s’il devient défaillant, la croissance fœtale n’est plus optimale, et notamment la formation et la maturation des gonades – qui se déroulent in utero –, ce qui peut affecter la fertilité à l’âge adulte. Ainsi le placenta est-il un acteur central de la programmation fœtale. Les adaptations fœto-placentaires aux perturbations de l’environnement maternel ont des conséquences sur la santé des descendants à l’âge adulte et sont une cause potentielle d’infertilité

Stress oxydatif chez les mammifères: effets sur la grossesse et la fonction placentaire

Dossier: de la conception à la naissance: le père et la mèreNational audienceL'oxygène est essentiel à la vie des organismes aérobies : il permet la respiration cellulaire et la synthèse d'adénosine triphosphate (ATP), mais il peut aussi devenir toxique pour les cellules : on parle alors du paradoxe de l'oxygène. Près de 90 % de l'oxygène est métabolisé en eau par les mitochondries tandis que les 10 % restants sont partiellement oxydés pour produire les espèces réactives de l'oxygène (Reactive Oxygen Species [ROS]) et les espèces réactives nitriques (Reactive Nitrogen Species [RNS]). La cellule produit des quantités physiologiques de ROS qui jouent un rôle majeur dans la signalisation cellulaire et dans la réponse immunitaire aux agents pathogènes. Lorsque cette production devient excessive et dépasse les capacités antioxydantes de la cellule, un déséquilibre se produit et induit un stress oxydatif. Le stress oxydatif est donc la résultante d'une augmentation de la production des ROS et d'un défaut des voies de détoxification, en particulier des enzymes antioxydantes. Cependant, l'expression des gènes des enzymes antioxydantes peut aussi être stimulée par le stress oxydatif. Dans le contexte de la gestation chez les mammifères, un niveau élevé de ROS peut induire une apoptose et des avortements ou alors, à des niveaux plus modérés, un dysfonctionnement cellulaire à l'origine de tératogenèse. Chez l'humain, les ROS sont fortement mis en cause dans les cas d'avortements spontanés précoces, de retard de croissance intra-utérin, de prééclampsie, de syndrome de Down et d'accouchements prématurés