Prenatal alcohol exposure is associated with changes in placental gene co-expression networks.

Alcohol consumption during pregnancy can result in a range of adverse postnatal outcomes among exposed children. However, identifying at-risk children is challenging given the difficulty to confirm prenatal alcohol exposure and the lack of early diagnostic tools. Placental surveys present an important opportunity to uncover early biomarkers to identify those at risk.

RNA-seq analysis reveals prenatal alcohol exposure is associated with placental inflammatory cells and gene expression.

Background: Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses.

Prioritization of potential causative genes for schizophrenia in placenta.

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits.

A Systematic Review of the Placental Translocation of Micro- and Nanoplastics.

Purpose Of Review: Despite increasing awareness of the ubiquity of microplastics (MPs) in our environments, little is known about their risk of developmental toxicity. Even less is known about the environmental distribution and associated toxicity of nanoplastics (NPs). Here, we review the current literature on the capacity for MPs and NPs to be transported across the placental barrier and the potential to exert toxicity on the developing fetus.

Ethnic disparities in ambient air and traffic-related pollution exposure and ethnic-specific impacts on clinical biomarker levels.

Background: Although characterizing the inequality in pollution exposure burden across ethnic groups and the ethnic-specific exposure associations is of great social and public health importance, it has not been systematically investigated in large population studies.

Methods: The UK Biobank data (N = 485, 806) of individual-level air ambient and traffic-related pollution exposure, biomarkers routinely used in clinical practice, genotype, life-style factors, and socioeconomic status were analyzed. Air pollution exposure estimates were compared among six genetically inferred ethnic groups.

Placental Gene Transcript Proportions are Altered in the Presence of Arsenic and Cadmium Exposures, Genetic Variants, and Birth Weight Differences.

arsenic and cadmium exposures are linked with reduced birth weight as well as alterations in placental molecular features. However, studies thus far have focused on summarizing transcriptional activity at the gene level and do not capture transcript specification, an important resource during fetal development to enable adaptive responses to the rapidly changing physiological conditions. In this study, we conducted a genome-wide analysis of the placental transcriptome to evaluate the role of differential transcript usage (DTU) as a potential marker of arsenic and cadmium exposure and fetal growth restriction.

PM exposure during pregnancy is associated with altered placental expression of lipid metabolic genes in a US birth cohort.

Inhalation of ambient PM2.5, shown to be able to cross the placenta, has been linked to adverse obstetric and postnatal metabolic health outcomes. The placenta regulates fetal growth and influences postnatal development via fetal programming.

Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain.

Despite several decades of research and prevention efforts, fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of neurodevelopmental disabilities worldwide. Animal and human studies have implicated fetal alcohol-induced alterations in epigenetic programming as a chief mechanism in FASD. Several studies have demonstrated fetal alcohol-related alterations in methylation and expression of imprinted genes in placental, brain, and embryonic tissue.

Placental gene network modules are associated with maternal stress during pregnancy and infant temperament.

Maternal psychosocial stress during pregnancy (MPSP) is a known contributor to maladaptive neurobehavioral development of the offspring; however, the underlying molecular mechanisms linking MPSP with childhood outcome remain largely unknown. Transcriptome-wide gene expression data were generated using RNA-seq from placenta samples collected in a multi-ethnic urban birth cohort in New York City (n = 129). Weighted gene co-expression network analysis (WGCNA) was used to characterize placental co-expression modules, which were then evaluated for their associations with MPSP and infant temperament.

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three.

Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies.

Preeclampsia is a multi-systemic syndrome that presents in approximately 5% of pregnancies worldwide and is associated with a range of subsequent postpartum and postnatal outcomes, including fetal growth restriction. As the placenta plays a critical role in the development of preeclampsia, surveying genomic features of the placenta, including expression of imprinted genes, may reveal molecular markers that can further refine subtypes to aid targeted disease management. In this study, we conducted a comprehensive survey of placental imprinted gene expression across early and late onset preeclampsia cases and preterm and term normotensive controls.

Maternal stress in relation to sex-specific expression of placental genes involved in nutrient transport, oxygen tension, immune response, and the glucocorticoid barrier.

Introduction: Murine models provide evidence that maternal stress during pregnancy can influence placenta morphology and function, including altered expression of genes involved in the maintenance and progression of pregnancy and fetal development. Corresponding research evaluating the impact of maternal stress on placental gene expression in humans is limited. We examined maternal stress in relation to placental expression of 17 candidate genes in a community-based sample.

Moderate prenatal stress may buffer the impact of Superstorm Sandy on placental genes: Stress in Pregnancy (SIP) Study.

The placenta plays a central role in the epigenetic programming of neurodevelopment by prenatal stress (PS), but this pathway is not fully understood. It difficult to study in humans because the conditions for intense, traumatic PS are almost impossible to create ethically. This study was able to capitalize on a 2012 disaster that hit New York, Superstorm Sandy, to examine the impact of traumatic stress on placental gene expression while also examining normative PS, and compare the two.

Placental Expression of Imprinted Genes, Overall and in Sex-Specific Patterns, Associated with Placental Cadmium Concentrations and Birth Size.

Background: Prenatal cadmium (Cd) exposure has been recognized to restrict growth, and male and female fetuses may have differential susceptibility to the developmental toxicity of Cd. Imprinted genes, which exhibit monoallelic expression based on parent of origin, are highly expressed in placental tissues. The function of these genes is particularly critical to fetal growth and development, and some are expressed in sex-specific patterns.

Maternal circadian disruption is associated with variation in placental DNA methylation.

Circadian disruption is a common environmental and occupational exposure with public health consequences, but not much is known about whether circadian disruption affects in utero development. We investigated whether maternal circadian disruption, using night shift work as a proxy, is associated with variations in DNA methylation patterns of placental tissue in an epigenome-wide association study (EWAS) of night shift work. Here, we compared cytosine-guanosine dinucleotide (CpG) specific methylation genome-wide of placental tissue (measured with the Illumina 450K array) from participants (n = 237) in the Rhode Island Child Health Study (RICHS) who did (n = 53) and did not (n = 184) report working the night shift, using robust linear modeling and adjusting for maternal age, pre-pregnancy smoking, infant sex, maternal adversity, and putative cell mixture.

Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity.

GWAS identified variants associated with birth weight (BW), childhood obesity (CO) and childhood BMI (CBMI), and placenta is a critical organ for fetal development and postnatal health. We examined the role of placental transcriptome and eQTLs in mediating the genetic causes for BW, CO and CBMI, and applied integrative analysis (Colocalization and MetaXcan). GWAS loci associated with BW, CO, and CBMI were substantially enriched for placenta eQTLs (6.

Intrauterine multi-metal exposure is associated with reduced fetal growth through modulation of the placental gene network.

Background: Intrauterine metal exposures and aberrations in placental processes are known contributors to being born small for gestational age (SGA). However, studies to date have largely focused on independent effects, failing to account for potential interdependence among these markers.

Objectives: We evaluated the inter-relationship between multi-metal indices and placental gene network modules related to SGA status to highlight potential molecular pathways through which in utero multi-metal exposure impacts fetal growth.