Epigenetic mechanisms in the placenta related to infant neurodevelopment

Abstract

As the 'third brain' the placenta links the developing fetal brain and the maternal brain enabling study of epigenetic process in placental genes that affect infant neurodevelopment. We described the characteristics and findings of the 17 studies on epigenetic processes in placental genes and human infant neurobehavior. Studies showed consistent findings in the same cohort of term healthy infants across epigenetic processes (DNA methylation, genome wide, gene and miRNA expression) genomic region (single and multiple genes, imprinted genes and miRNAs) using candidate gene and genome wide approaches and across biobehavioral systems (neurobehavior, cry acoustics and neuroendocrine). Despite limitations, studies support future work on molecular processes in placental genes related to neurodevelopmental trajectories including implications for intervention.

Keywords: HPA axis; NICU network neurobehavioral scale (NNNS); cry acoustics; development; epigenetics; fetal programming; infant; neurobehavior; placenta; trajectories.

Figure 1.. NICU network neurobehavioral scale profiles were calculated using a recursively partitioned mixture model algorithm using the NICU network neurobehavioral scale summary scores (x-axis).

The scores are plotted as standard scores or standard deviation units (y-axis). The profiles are mutually exclusive subgroups of infants, ‘typologies’, with distinct patterns of performance across the summary scores. Data taken from [22].

Figure 2.. Digitized spectrogram plot.

The plot is generated using a computerized acoustical analysis system. Time (∼2 s) is on the x axis, Hz is on the y axis. The vertical red-yellow spikes are individual vocal utterances of the cry. The clarity of the cry signal ranges from ‘more’ (yellow) or phonation to ‘less’ (red) or dysphonation. Spaces in between the utterances are pauses or breathes.

Figure 3.. Venn diagram of similarities from genes from the CpGs with highly significant correlations and NICU network neurobehavioral scale scores.

Data taken from [26].

Figure 4.. Heatmap of expression for ten genes used to assign membership to NICU network neurobehavioral scale clusters.

Average scores of infant stress abstinence, quality of movement, asymmetrical reflexes and nonoptimal reflexes differed across the gene expression-based clusters. Infants in gene expression clusters 2 and 3 exhibited more signs of stress and abstinence, reduced quality of movement and increased signs of asymmetrical and nonoptimal reflexes. Data taken from [24].