Placenta DNA methylation levels of the promoter region of the leptin receptor gene are associated with infant cortisol

• Type of Material: Article
• Authors: Brie M. Reid, Brown University; Nicki L. Aubuchon-Endsley, University of Tulsa; Audrey Tyrka, Brown University; Carmen J. Marsit, Emory University; Laura Strod, Brown University
• Language: English
• Date: 2023-04-20
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2023 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.psyneuen.2023.106119
• Title of Journal or Parent Work: Psychoneuroendocrinology
• Volume: 153
• Start Page: 106119
• Grant/Funding Agency: National Institute of General Medical Sciences; National Institute on Drug Abuse; National Institute of Mental Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences
• Grant/Funding Information: The authors thank the families and research assistants who make our research possible. This research was supported by grants from the National Institute of Mental Health [R01MH079153], the National Institute on Drug Abuse [5R01DA044504], the National Institute of Environmental Health Sciences [R24ES028507 and P30ES019776], and the National Institute of General Medical Sciences [1P20GM139767] to LRS. BMR was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD101392 and K99HD109373]. P20GM139767, R01HD095837, and R01HD086487 supported ART’s effort.
• Keywords: leptin; hypothalamic-pituitary-adrenocortical a; epigenetics; newborn
• Subject - Topics: Stress (Psychology); Epigenetics; Placenta

Abstract

The intrauterine environment and early life stress regulation are widely recognized as an early foundation for lifelong physical and mental health. Methylation of CpG sites in the placenta represents an epigenetic modification that can potentially affect placental function, influence fetal development, and ultimately impact the health of offspring by programming the hypothalamic-pituitary-adrenal (HPA) axis stress response during prenatal development. Leptin, an adipokine produced by the placenta, is essential for energy homeostasis. It is also epigenetically regulated by promoter DNA methylation. Mounting evidence suggests that leptin also affects the stress response system. Though heterogeneity in the early stress response system may influence life-long mental and physical health, few studies explicitly examine the heterogeneity in the newborn stress response system. Less is known about leptin's association with the human hypothalamic-pituitary-adrenocortical (HPA) axis early in life. This study sought to serve as a proof of concept study investigating the relationship between newborn cortisol output trajectories and placental leptin DNA methylation in 117 healthy newborns from socioeconomically and racially- and ethnically-diverse families. We characterized heterogeneity in newborn cortisol output during the NICU Network Neurobehavioral Scales exam in the first week of life with latent growth mixture models. We then evaluated whether leptin promoter (LEP) methylation in placental samples was associated with newborn cortisol trajectories. Our findings suggest that increased placental LEP methylation, which corresponds to decreased leptin production, is associated with infant cortisol trajectories marked by increased cortisol output in the NNNS exam. These results provide important insights into the role of placental leptin DNA methylation in human newborn HPA axis development and subsequent developmental origins of health and disease processes.