19945 - 2 - The Placenta and Human Developmental Programming

Developmental programming of the fetus is a phenomenon that has profound implications for the health of individuals and societies. The term describes the process by which gene expression in the fetus is influenced by the intrauterine environment, such that the structure of major organs and the homoeostatic points of metabolic and endocrine systems are set for life. Through this mechanism, perturbations in the intrauterine experience that affect development may predispose to a spectrum of adult diseases, depending on the system principally affected. Thus, in a recent review the National Institute of Child Health concluded that ‘coronary heart disease, the number one cause of death among adult men and women, is more closely related to low birth weight than to known behavioural risk factors’. The list of diseases continues to grow, and now also includes diverse metabolic, neoplastic and neurological disorders. This striking effect first came to light through epidemiological studies of men in Hertfordshire, UK, who had died from cardiovascular disease. Through the records maintained by the midwives attending the births of these men it was possible to show that death rates from the disease fell across the normal range of birth weight. In a later study of blood pressure levels among men and women in Preston, UK, it was possible to relate birth weight to the weight of the placenta. People with small placentas and people with large placentas in relation to their birth weights had the highest blood pressure levels. Although these data highlighted the importance of the fetoplacental relationship to developmental programming, the mechanistic role of the placenta in the phenomenon has received little attention to date. This is a remarkable oversight, given that the placenta evolved to support the fetus in utero, and must therefore reasonably be expected to be a key determinant of fetal growth. This book records the proceedings of a scientific meeting convened to rectify this situation. The meeting, held over two days in Cambridge in December 2009, brought together invited experts from a wide variety of disciplines to present and discuss their data in depth under the skilful and diplomatic guidance of the Chair, Professor Sir Robert Boyd. The contributions presented here explore our current knowledge of the ways in which various aspects of placental development and function may influence fetal programming, and aim to promote further scientific research in their respective fields. When structuring the meeting, we aimed to consider the development of the placenta from the level of molecular genetics through to epidemiological biomarkers, and from pre-conception through to maturity, with the emphasis being placed on human data. The starting point of the meeting was that changes in the shape of the placental surface, whether it is round or oval, are related to developmental programming. Little attention has been paid to the importance of placental shape in recent years, or to its determinants. What is so striking, however, is that placental shape changed radically over the 20-year period of the Helsinki study, indicating that it is surprisingly plastic and responsive to intrauterine cues. Equally, it is not known whether the tissues along the major and minor axes of the placenta perform the same functional roles. The placenta has a wide variety of functions, including passive and active transport, hormone synthesis, metabolic regulation, acting as a selective barrier to maternal hormones and as an immunological shield. We must therefore be precise when we talk in terms of placental efficiency and insufficiency, and refer to the specific function being monitored. Morphologically, placental development starts at the time of implantation, but can of course be