Placental programming of chronic diseases, cancer and lifespan: A review

Abstract

Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other influences during development set the body's organs and systems for life. The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size.

The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required. We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity.

Introduction

Small body size at birth is now known to predict a range of disorders in adult life including cardiovascular disease, type 2 diabetes and certain cancers and infections [1], [2]. These associations are thought to reflect “fetal programming,” the phenomenon whereby nutrition and other influences during development set the structure of the body's organs and the function of it's systems for life. A large body of experimental evidence from animals demonstrates this phenomenon and allows examination of the underlying mechanisms [3]. During development there are critical periods during which a system or organ has to mature. These periods are brief; they occur at different times for different systems; and for most organs and systems in the human body they occur in utero. During critical periods organs and systems are susceptible to being programmed. The thesis of this review is that normal variations in the processes of development lead to variations in the supply of nutrients during critical periods [2]. These variations may set a small number of key systems, including antioxidant defences, inflammatory responses, the immune system, the number and quality of stem cells, neuroendocrine settings and the balance of the autonomic nervous system.

Body size at birth is correlated with placental size. Large babies generally have large placentas. Fig. 1, taken from a large series of singletons born at term Saudi Arabia, shows, however, that at any birthweight there is a wide range of placental weight [4]. A baby's nutrition depends on both the placenta's ability to transfer nutrients from mother to baby and on the mother's nutritional state. Babies do not depend only on their mothers' diets during pregnancy: that would be too dangerous a strategy [5]. Rather, they also depend on her metabolism. This is the product of her lifetime nutrition and is reflected in her height and weight [6]. A priori it is likely that the contribution of placental size to fetal programming will depend on the mother's nutritional history. Therefore, in many studies, the effects of placental size on later disease have been examined within different categories of mother's body size.