The omniscient placenta: Metabolic and epigenetic regulation of fetal programming

Abstract

Fetal development could be considered a sensitive period wherein exogenous insults and changes to the maternal milieu can have long-term impacts on developmental programming. The placenta provides the fetus with protection and necessary nutrients for growth, and responds to maternal cues and changes in nutrient signaling through multiple epigenetic mechanisms. The X-linked enzyme O-linked-N-acetylglucosamine transferase (OGT) acts as a nutrient sensor that modifies numerous proteins to alter various cellular signals, including major epigenetic processes. This review describes epigenetic alterations in the placenta in response to insults during pregnancy, the potential links of OGT as a nutrient sensor to placental epigenetics, and the implications of placental epigenetics in long-term neurodevelopmental programming. We describe the role of placental OGT in the sex-specific programming of hypothalamic-pituitary-adrenal (HPA) axis programming deficits by early prenatal stress as an example of how placental signaling can have long-term effects on neurodevelopment.

Impact of maternal prenatal smoking on fetal to infant neurobehavioral development

“…Sex differences have been documented in human and animal models at multiple steps within fetal programming pathways including maternal-fetal glucocorticoid regulation, placental structure and function, and in offspring neurodevelopmental outcomes following prenatal perturbations (Bale, 2011; J. A. DiPietro et al, 2011; Nugent & Bale, 2015; Rosenfeld, 2015; Sandman, Glynn, & Davis, 2013). Sandman and colleagues have proposed an early-life viability-later-life vulnerabilty trade-off for males and females.…”

Association of prenatal and early childhood stress with reduced lung function in 7-year-olds

“…For example, recent analyses in the Lifestyle and environmental factors and their Influence on Newborns Allergy risk (LINA) study reported differentially methylated regions in calcium- and Wnt-signaling pathways involved in lung maturation prenatally among children exposed to increased prenatal stress who went on to develop wheeze 54 . Other evidence indicates that stress-induced epigenetic changes that influence development can be sex specific 55,56 .…”

Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment

“…At the interface of maternal experience and the developing fetus lies the placenta, a tissue that serves as a gatekeeper of maternal signals, admitting critical nutrients and gasses from maternal circulation while blocking pathogenic intruders including viruses and bacteria (51). Here we focus our discussion on the evidence for epigenetic mechanisms in the placenta to promote sex-specific offspring responses to prenatal stress.…”

“…Here we focus our discussion on the evidence for epigenetic mechanisms in the placenta to promote sex-specific offspring responses to prenatal stress. For additional discussion on the involvement of the placenta in transmitting maternal signals to the developing fetal brain see reviews (51–54). …”