Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study

Abstract

The placental epigenome regulates processes that affect placental and fetal development, and could be mediating some of the reported effects of maternal choline supplementation (MCS) on placental vascular development and nutrient delivery. As an extension of work previously conducted in pregnant mice, the current study sought to explore the effects of MCS on various epigenetic markers in the placenta. RNA and DNA were extracted from placentas collected on embryonic day 15.5 from pregnant mice fed a 1X or 4X choline diet, and were subjected to genome-wide sequencing procedures or mass-spectrometry-based assays to examine placental imprinted gene expression, DNA methylation patterns, and microRNA (miRNA) abundance. MCS yielded a higher (fold change = 1.63–2.25) expression of four imprinted genes (Ampd3, Tfpi2, Gatm and Aqp1) in the female placentas and a lower (fold change = 0.46–0.62) expression of three imprinted genes (Dcn, Qpct and Tnfrsf23) in the male placentas (false discovery rate (FDR) ≤ 0.05 for both sexes). Methylation in the promoter regions of these genes and global placental DNA methylation were also affected (p ≤ 0.05). Additionally, a lower (fold change = 0.3; Punadjusted = 2.05 × 10−4; FDR = 0.13) abundance of miR-2137 and a higher (fold change = 1.25–3.92; p < 0.05) expression of its target genes were detected in the 4X choline placentas. These data demonstrate that the placental epigenome is responsive to maternal choline intake during murine pregnancy and likely mediates some of the previously described choline-induced effects on placental and fetal outcomes.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring

“…Studies also demonstrate that over a quarter of gene expression changes in offspring exposed to maternal HF feeding are associated with DNA methylation alterations [14], suggesting that epigenetic modifications early in life are likely contributors to later metabolic abnormalities. Choline, as a methyl donor, has been demonstrated to alter global and/or site-specific DNA methylation in both human and mouse placentas [15,16] and offspring tissues [16][17][18][19]. Hence, MCS may also interact with maternal HF feeding to influence offspring metabolism via an epigenetic mechanism.…”

Long‐term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease

“…donor for gene expression regulation through epigenetic programming (5)(6)(7)(8). Choline is also a key substrate in the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, from which several structural membrane phospholipids, including sphingomyelin and phosphatidylcholine (PC), are generated (9,10).…”

DNA methylation pattern of the goat &lt;i&gt;PITX1&lt;/i&gt; gene and its effects on milk performance

“…Comparisons of the methylation difference at each CpGdinucleotide locus, the entire CpG island between the low and high groups for each milk trait, and the methylation status of mammary gland tissue from dry and lactation periods were analyzed using the Fisher's exact test (χ 2 -test) as previously described (Lan et al, 2013a).…”

“…The number of positive inserts for each pool sent for sequencing was around 10, according to the efficiency of ligation and transformation. The methylation status for the CpG island and each CpG-dinucleotide locus was measured by sequencing, and alignment analyses were carried out using DNAMAN software (version 7.0, Lynnon Biosoft, Vaudreuil, Quebec, Canada) (Lan et al, 2013a).…”

“…Over the past decade, the influences of genetic variations on milk performance in animals have been extensively studied (Koufariotis et al, 2018). Recently an increasing number of studies have demonstrated that nutritional or environmental changes contribute to changes in inheritable epigenetic modifications, such as DNA methylation (Lan et al, 2013a;Chavatte-Palmer et al, 2018;Kwan et al, 2018;Yuan et al, 2018). As one of the most important and common types of epigenetic modification, DNA methylation plays a significant role in regulating biological processes such as milk production and organ development (Hwang et al, 2017;Fleming et al, 2018;Jessop et al, 2018).…”