Placental Origins of Chronic Disease.

Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions.The authors thank the various funding agencies that have generously supported their research over the years; GJB, the Medical Research Council, the Wellcome Trust and Action Medical Research; ALF, the Biotechnology and Biological Sciences Council, the Medical Research Council and the Wellcome Trust; KLT, the National Institutes of Child Health and Human Development, the Nation Heart Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the American Heart Association and the M. Lowell Edwards Endowment.This is the author accepted manuscript. The final version is available from the American Physiological Society via https://doi.org/10.1152/physrev.00029.201

Nutrition in Pregnancy: Volume I

Maternal nutrition during pregnancy is of considerable interest to women, their partners and their health care professionals. In developing countries, maternal undernutrition is a major concern. However, with the increased prevalence of abundant high calorie diets, their impact upon pregnancy outcome is of concern. In addition to the amount of nutrition available and its macronutrient composition within a diet, there is emerging evidence highlighting important roles for the lesser studied micronutrients. Added to this complexity is the distinction between maternal and fetal nutrition and the impact the placenta plays in nutrient metabolism and overall nutrient supply to the fetus. Together, these many variables contribute to placental development and function, fetal growth, and, where placental/fetal nutrition and growth is compromised, through poor maternal diet, and/or diet induced alterations in placental metabolism, the impact is dramatic and can lead to lifelong implications for the offspring. This Special Issue book aims to highlight research in many of these areas

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

Intergenerational effects of high fat diet: exploring mechanisms in germ cells

The prevalence of obesity is increasing each year, likely due to altered diet and a sedentary lifestyle. However, some epidemiological data suggests that parental and grandparental environments may also impact upon weight gain, metabolic health and mortality. This non-genetic inheritance has been reproduced in some experimental animal studies. The mechanisms are, however, unknown. One hypothesis has been that environmental exposures perturb germ cell development. Changes to the germ cell epigenome are an example of one such alteration. In this thesis, epigenetic mechanisms are explored in rodent and primate male germ cells throughout development. The conservation of global methylation patterns, expression of DNA methyltransferases and of key histone modifications is demonstrated in rat, marmoset and human tissue demonstrating mechanisms are in place that might be disrupted by environmental exposures either in utero or during post-natal development. A rat model of parental high fat diet (HFD) exposure is established and phenotype explored in two generations of offspring. Maternal HFD results in weight gain in male and female offspring and paternal HFD in weight gain in just female offspring. Grandpaternal exposure to HFD via the maternal line has the greatest impact on the second generation where, in males, increased weight, adiposity, reduced insulin sensitivity and an increased luteinising hormone to testosterone ratio were found. Given that postnatal exposure in males resulted in adverse metabolic health in grand offspring, the exposed germ cells were interrogated by RNA and smallRNA-sequencing. HFD exposure did not alter the germline transcriptome suggesting an alternative mechanism to be responsible for the intergenerational effects observed. Thus, HFD perturbs metabolic health in two generations of rats in a grand-parent and sex specific manner but does not affect the germ cell transcriptome