The prospective associations of fetal growth-related pregnancy complications with subsequent breastfeeding duration and markers of human milk production.

Background: The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding (BF) success.

Objectives: We examined whether fetal growth-related pregnancy complications were associated with earlier BF cessation and changes in the concentrations of human milk biomarkers of low milk production.

The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production.

Background: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive.

Objectives: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production.

Methods: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum.

Cell type-specific DNA methylation in neonatal cord tissue and cord blood: a 850K-reference panel and comparison of cell types.

Accounting for cellular heterogeneity is essential in neonatal epigenome-wide association studies (EWAS) performed on heterogeneous tissues, such as umbilical cord tissue (CT) or cord blood (CB). Using a reference-panel-based statistical approach, the cell type composition of heterogeneous tissues can be estimated by comparison of whole tissue DNA methylation profiles with cell type-specific DNA methylation signatures. Currently, there is no adequate DNA methylation reference panel for CT, and existing CB panels have been generated on lower coverage Infinium HumanMethylation450 arrays.

Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples.

Interindividual variability in the epigenome has gained tremendous attention for its potential in pathophysiological investigation, disease diagnosis, and evaluation of clinical intervention. DNA methylation is the most studied epigenetic mark in epigenome-wide association studies (EWAS) as it can be detected from limited starting material. Infinium 450K methylation array is the most popular platform for high-throughput profiling of this mark in clinical samples, as it is cost-effective and requires small amounts of DNA.

Germline and somatic imprinting in the nonhuman primate highlights species differences in oocyte methylation.

Genomic imprinting is an epigenetic mechanism resulting in parental allele-specific gene expression. Defects in normal imprinting are found in cancer, assisted reproductive technologies, and several human syndromes. In mouse models, germline-derived DNA methylation is shown to regulate imprinting.

Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.

CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights.

Infinium monkeys: Infinium 450K array for the Cynomolgus macaque (Macaca fascicularis).

The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is an important disease model; however, its genome sequence is only recently published, and few tools exist to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybridization array designed to the human genome, the relative conservation between the macaque and human genomes makes its use in macaques feasible.

The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment.

Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions.

Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus.

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.

Background: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.

Alternative splicing in self-renewal of embryonic stem cells.

Much of embryonic stem cell biology has focused on transcriptional expression and regulation of genes that could mediate its unique potential in self-renewal or pluripotency. In alignment with our present understanding on the genetic, protein, and epigenetic factors that may direct cell fate, we present a short overview of the often overlooked contribution of alternative splice variants to regulatory diversity. Progressing beyond the limitations of a fixed genomic sequence, alternative splicing offers an additional layer of complexity to produce protein variants that may differ in function and localization that can direct embryonic stem cells to specific differentiation pathways.

In silico tandem affinity purification refines an Oct4 interaction list.

Introduction: Octamer-binding transcription factor 4 (Oct4) is a master regulator of early mammalian development. Its expression begins from the oocyte stage, becomes restricted to the inner cell mass of the blastocyst and eventually remains only in primordial germ cells. Unearthing the interactions of Oct4 would provide insight into how this transcription factor is central to cell fate and stem cell pluripotency.

Transcriptional repression in ES cells.

The dynamics of embryonic stem cell pluripotency is orchestrated by an interplay of transcriptional and epigenetic regulation in a systematic and modular manner. While the ES cell stage is marked by multiple loci with bivalent chromatin marks that prepare genes for imminent activation on differentiation, this open chromatin conformation is tempered by repressive machinery that prevent premature expression of key developmental genes. This review serves to highlight key ES transcription factors and their known links to the epigenetic machinery via known protein complexes.