Genomic Imprinting in Human Placenta

Abstract

This book contains the total of 19 chapters, each of which is written by one or several experts in the corresponding field. The objective of this book is to provide a comprehensive and most updated overview of the human placenta, including current advances and future directions in the early detection, recognition, and management of placental abnormalities as well as the most common placental structure and functions, abnormalities, toxicology, infections, and pathologies. It also includes a highly controversial topic, therapeutic applications of the human placenta. A collection of articles presented by active investigators provides a clear update in the area of placental research for medical students, nurse practitioners, practicing clinicians, and biomedical researchers in the fields of obstetrics, pediatrics, family practice, genetics, and others who may be interested in human placentas.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

“…Rapid advancements in the discovery of integrated regulation of neuropeptide homeostasis within the brain and placenta [63, 64] have led to the concept that the placenta may be like a “third brain” linking the developed (maternal) and developing (fetal) brains [64, 65]. Maternal perturbations are conveyed to the fetus via the placenta, in the expression of transporters that regulate the flux of glucose, amino acids, and vitamins required for growth and development [66]. Thus, the placenta serves as the “master regulator” in utero and plays a highly functional role in shaping fetal development [65].…”

“…Fetoplacental development begins with a complex and highly coordinated set of epigenetic events that take place few hours after fertilization and before the implantation of the fertilized egg [66–68]. During this relatively short but very active window an almost complete reprogramming of the genome methylation takes place accompanied by a reorganization of the histone coding [68, 69].…”

“…At this stage, specific genomic regions carrying a unique set of multilayer epigenetic signals inherited from the germline, known as Imprinting Control Regions (ICRs), are spared this epigenome reprogramming wave (Fig. 1) [66, 70]. ICRs control the allele-specific expression of clusters of over 100 genes (or about 1% of the protein-coding genes) distributed across the human genome.…”

Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity

“…10,11 These findings lend support to the ''Barker hypothesis'' or the theory of developmental origins of health and disease, which hypothesizes that antenatal environmental factors lead to alterations in fetal programming that can induce permanent biological and physiologic changes later in life. [12][13][14][15][16][17][18][19] It has been hypothesized that critical windows of susceptibility exist during pregnancy, 20,21 and many of the acquired adverse effects related to the intrauterine environment result in epigenetic alterations such as changes in DNA methylation. 22 Although recent evidence has begun to show a longterm association between maternal GDM and/or preeclampsia and offspring development at birth and in childhood, [23][24][25] the underlying biological mechanism is not yet understood.…”

Maternal residential air pollution and placental imprinted gene expression

“…The highly controlled pattern of expression of these genes is critical to normal development and plays a particularly important role in the placenta functioning (Fowden et al 2006; Miozzo and Simoni 2002; Reik and Walter 2001). For example, loss of genomic imprinting (LOI) early in development can lead to placental and fetal growth restriction (Lambertini et al 2012a), and recent studies have shown that even relatively modest differences in imprinted gene expression are associated with fetal growth/birth weight (Kappil et al 2015a; Lambertini et al 2012b). Moreover, in both human and animal studies imprinted gene expression has been associated with exposure to a number of environmental exposures, including, maternal nutrition, alcohol use, tobacco use, and BPA exposure, and imprinted gene expression has been highlighted as a potentially useful environmental sensor (Kappil et al 2015b).…”