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. 2020 Mar;82(3):e23101.
doi: 10.1002/ajp.23101. Epub 2020 Feb 5.

Maternal weight affects placental DNA methylation of genes involved in metabolic pathways in the common marmoset monkey (Callithrix jacchus)

Laren Narapareddy  1 , Derek E Wildman  2 , Don L Armstrong  3 , Amy Weckle  4 , Aleeca F Bell  5 , Crystal L Patil  5 , Suzette D Tardif  6 , Corinna N Ross  7 , Julienne N Rutherford  5
Affiliations

Maternal weight affects placental DNA methylation of genes involved in metabolic pathways in the common marmoset monkey (Callithrix jacchus)

Laren Narapareddy et al. Am J Primatol. 2020 Mar.

Abstract

Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including the regulation of glycolytic and lipid metabolic processes pathways.

Keywords: developmental programming; epigenetics; maternal metabolism; non-human primate; obesity.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Workflow of the analytical strategy used to describe DNA methylation (DNAm) in the marmoset placenta and to identify genes and gene pathways that are associated with maternal weight during gestation
Figure 2
Figure 2
Schematic timeline of marmoset fetoplacental development across 143 days of gestation, indicating critical time points (•) of the model. The most rapid period of placental growth occurs between Days 0 and 100, at which time placental growth is completed. Fetal growth is slow during early gestation until Day 60 when it begins to rapidly increase through Day 120. Day 90 is the midway point of this growth rate period. The most rapid increase in fetal growth rate occurs after Day 120 and at this time point, twin growth rate exceeds triplet growth rate. From Riesche et al. (2018; permissions will be requested)
Figure 3
Figure 3
Distribution of methylation across all CpG sites. Histogram of M‐Value. M = −7 indicated fully unmethylated CpG sites, M = 0 indicates hemi‐methylated CpG sites, and M = 7 indicates fully methylated CpG sites
Figure 4
Figure 4
Comparison of the number of completely methylated (▪) and completely unmethylated (▪) CpG sites at specific distances within (<3 kb) and outside (≥3 kb) the promoter region
Figure 5
Figure 5
Current model demonstrating the potential role of placental DNA methylation (DNAm) in developmental programming of obesity. Maternal weight influences ovulation number and is related to placental DNAm patterns in gene pathways involved in energy metabolism and homeostasis. Downstream effects of altered DNAm in these pathways likely leads to physiological adaptations in the fetus with consequences for long‐term metabolic health
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