Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

A systematic review of methods to assess intake of fruits and vegetables among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Evidence suggests that health benefits are associated with consuming recommended amounts of fruits and vegetables (F&V), yet standardised assessment methods to measure F&V intake are lacking. The current review aims to identify methods to assess F&V intake among children and adults in pan-European studies and inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed F&V intake were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children or adults. The review identified fifty-one pan-European studies which assessed F&V intake. The FFQ was the most commonly used (n 42), followed by 24 h recall (n 11) and diet records/diet history (n 7). Differences existed between the identified methods; for example, the number of F&V items on the FFQ and whether potatoes/legumes were classified as vegetables. In total, eight validated instruments were identified which assessed F&V intake among adults, adolescents or children. The current review indicates that an agreed classification of F&V is needed in order to standardise intake data more effectively between European countries. Validated methods used in pan-European populations encompassing a range of European regions were identified. These methods should be considered for use by future studies focused on evaluating intake of F&V.

A systematic review of methods to assess intake of sugar-sweetened beverages among healthy European adults and children: a DEDIPAC (DEterminants of DIet and Physical Activity) study

Research indicates that intake of sugar-sweetened beverages (SSB) may be associated with negative health consequences. However, differences between assessment methods can affect the comparability of intake data across studies. The current review aimed to identify methods used to assess SSB intake among children and adults in pan-European studies and to inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods suitable for use in future European studies. A literature search was conducted using three electronic databases and by hand-searching reference lists. English-language studies of any design which assessed SSB consumption were included in the review. Studies involving two or more European countries were included in the review. Healthy, free-living children and adults. The review identified twenty-three pan-European studies which assessed intake of SSB. The FFQ was the most commonly used (n 24), followed by the 24 h recall (n 6) and diet records (n 1). There were several differences between the identified FFQ, including the definition of SSB used. In total, seven instruments that were tested for validity were selected as potentially suitable to assess SSB intake among adults (n 1), adolescents (n 3) and children (n 3). The current review highlights the need for instruments to use an agreed definition of SSB. Methods that were tested for validity and used in pan-European populations encompassing a range of countries were identified. These methods should be considered for use by future studies focused on evaluating consumption of SSB.

Youth-Physical Activity Towards Health: evidence and background to the development of the Y-PATH physical activity intervention for adolescents

Background: Despite known benefits of regular physical activity for health and well-being, many studies suggest that levels of physical activity in young people are low, and decline dramatically during adolescence. The purpose of the current research was to gather data on adolescent youth in order to inform the development of a targeted physical activity intervention. Methods: Cross-sectional data on physical activity levels (using self report and accelerometry), psychological correlates of physical activity, anthropometic characteristics, and the fundamental movement skill proficiency of 256 youth (53% male, 12.40 ± 0.51 years) were collected. A subsample (n = 59) participated in focus group interviews to explore their perceptions of health and identify barriers and motivators to participation in physical activity. Results: Findings indicate that the majority of youth (67%) were not accumulating the minimum 60 minutes of physical activity recommended daily for health, and that 99.5% did not achieve the fundamental movement skill proficiency expected for their age. Body mass index data showed that 25% of youth were classified as overweight or obese. Self-efficacy and physical activity attitude scores were significantly different (p < 0.05) between low, moderate and high active participants. Active and inactive youth reported differences in their perceived understanding of health and their barriers to physical activity participation, with active youth relating nutrition, exercise, energy and sports with the definition of ‘being healthy’, and inactive youth attributing primarily nutritional concepts to ‘being healthy’. Conclusions: Data show a need for targeting low levels of physical activity in youth through addressing poor health related activity knowledge and low fundamental movement skill proficiency. The Y-PATH intervention was developed in accordance with the present study findings; details of the intervention format are presented.

Development of an antigen-driven colitis model to study presentation of antigens by antigen presenting cells to T cells

Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG-/-recipients) are reconstituted with naive CD4+ T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4+ T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG-/- hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria.

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.