Placenta-imprinted gene expression association of infant neurobehavior

Abstract

Objective: To identify links between altered gene imprinting in the placenta and infant neurobehavioral profiles.

Study design: Quantitative reverse-transcription polymerase chain reaction was used to examine the expression of 22 imprinted candidate genes in a series of 106 term human primary placenta tissues. The expression pattern uncovered was associated with Neonatal Intensive Care Unit Network Neurobehavioral Scales summary scores in the corresponding infants. Clustering of the expression data was used to define distinct classes of expression.

Results: Significant associations were identified between classes of expression and the Neonatal Intensive Care Unit Network Neurobehavioral Scales quality of movement (P = .02) and handling (P = .006) scores. Multivariate regression demonstrated an independent effect of imprinted gene expression profile on these neurobehavioral scores after controlling for confounders.

Conclusion: These results suggest that alterations in imprinted gene expression in the placenta are associated with infant neurodevelopmental outcomes, and suggest a role for the placenta and genomic imprinting in the placenta beyond intrauterine growth regulation.

Figure 1

Correlation matrix of gene expression between imprinted genes in human placenta samples (n=106). Gene names and median expression levels are given in rows, and the spearman rank correlation between the expression of these genes is provided as a heatmap.

Figure 2

Gaussian recursively partitioned mixture models, a hierarchical clustering, based on imprinted gene expression identifying 4 distinct classes of expression signature. Samples are in rows and the expression of the 22 imprinted genes examined is shown by the heatmap in column. The dendrogram depicts the splitting of the samples into 4 classes, which are separated on the heatmap by red lines and are labeled as Classes 1 to 4.

Figure 3

Boxplots of the expression of each of the 22 imprinted genes in each of the recursively partitioned mixture model classes. Boxes represent 25^th and 75^th percentile, the dark horizontal line the median value, and the whiskers the 5^th and 95^th percentile.

Figure 4

Scatterplots of NICU Network Neurobehavioral Scales scores by gene-expression based recursively partitioned mixture models. The distribution of scores for (A) quality of movement, (B) attention, (C) arousal, (D) hypertonicity, (E) excitability, (F) stress/abstinence, (G) self-regulation, (H) non-optimal reflexes, and (I) handling are examined across each class, and the P-values provided are based on a non-parametric permutation-based Kruskal-Wallis test of differences across groups.