Individual variation in organ histogenesis as a causative factor in the developmental origins of health and disease: Unnoticed congenital anomalies?

Abstract

Morphological studies of congenital anomalies have mainly focused on abnormal shape (i.e. malformation) and thus on disturbed organogenesis. However, in regard to postnatal functions of organs that develop through branching mechanisms, organ size is another important morphological feature. These organs consist of a large number of structural and functional units, such as nephrons in the kidney, and the total number of these units, that is approximately proportional to the organ size, has been shown to vary widely among individuals. Organ‐specific cells are differentiated and organized to form structural units and realize organ‐specific functions during the histogenetic period (i.e. from mid‐gestation to the early postnatal period). The total number of units is attained at the end of histogenesis and determines the total functional capacity, including the functional reserve of the organ, and thus may be related to predispositions to postnatal organ‐based diseases, because the functional reserve decreases during the course of life and eventually become short of the minimum requirement of each organ. Therefore, it may be hypothesized that a smaller number of units of organs at the end of histogenesis is one of the predisposing factors for postnatal diseases (i.e. a form of unnoticed but late‐manifested congenital anomalies), in this era of extended longevity. However, the mechanisms that control the total number of units in each organ during histogenesis and the possible relationship among the numbers of units in different organs remain unknown. Here, we review our trials based on the above hypothesis in order to (1) mathematically analyze the morphometric data of the different organs in fetuses to elucidate relationship among developing organs, (2) analyze the developing neuro‐immuno‐endocrine network as a series of mechanisms to systemically correlate the histogenesis of multiple organs, and (3) examine the maternal environment, including dietary fat, as a factor to influence histogenesis and thus the predisposition to type 1 diabetes.

Adrenocorticotropic tumor cells transplanted into mouse embryos affect pancreatic histogenesis

“…ACTH and glucocorticoid are apparently among the critical molecules in the neuro‐immuno‐endocrine network, which intricately controls pleiotropic functions in adults and may influence the histogenesis of multiple organs during prenatal life (Otani et al . 2010).…”

“…2010). However, diseases in adults are mostly due to functional disorders in various individual combinations of organs, whereas the epigenetic and other metabolic mechanisms are systemic and thus have not yet been well correlated with concrete patterns of organ dysfunction that are specific to each individual (Solomons 2009; Otani et al . 2010).…”

“…Lower birth weight, including that caused by food restriction, has been shown to reduce the sizes of organs, such as the kidney (Cameron and Demerath 2002; Ross and Beall 2008), and has been thought to be related to an increased risk of postnatal diseases, such as hypertension. Furthermore, it has been documented that, even in fetuses of nearly the same body size, there are wide individual variations in the sizes of organs, such as the pancreas (Otani et al . 2010).…”

“…This suggests that not only the total amount of nutrition and/or overall ratios of nutritional compositions but also more intricate mechanisms control organ size; that is, the total number of structural and functional units during histogenesis, which may also be correlated with the incidence, onset, and clinical course of postnatal organ‐based diseases (Kagohashi et al . 2010; Otani et al . 2010).…”

“…This is because each organ's functional reserve decreases during the course of life and eventually becomes short of the minimum requirement for daily life. We therefore hypothesized that, in this era of extended longevity, a smaller number of units of organs at the end of histogenesis is one of the predisposing factors for postnatal diseases (Otani et al . 2010).…”