Identification of a DNA methylation signature in whole blood of newborn guinea pigs and human neonates following antenatal betamethasone exposure.

Antenatal corticosteroids (ACS) are administered where there is risk of preterm birth to promote fetal lung development and improve perinatal survival. However, treatment may be associated with increased risk of developing neurobehavioural disorders. We have recently identified that ACS results in significant changes to DNA methylation patterns in the newborn and juvenile prefrontal cortex (PFC) of exposed guinea pig offspring.

Prenatal maternal glucocorticoid exposure modifies sperm miRNA profiles across multiple generations in the guinea-pig.

Maternal stress and glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain.

Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission.

Approximately 1%-3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring.

DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life.

Synthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes.

Prenatal Glucocorticoid Exposure Results in Changes in Gene Transcription and DNA Methylation in the Female Juvenile Guinea Pig Hippocampus Across Three Generations.

Synthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery, to mature the fetal lung and decrease neonatal morbidity. sGC also profoundly affect the fetal brain. The hippocampus expresses high levels of glucocorticoid (GR) and mineralocorticoid receptor (MR), and its development is affected by elevated fetal glucocorticoid levels.

Antenatal Glucocorticoid Exposure Results in Sex-Specific and Transgenerational Changes in Prefrontal Cortex Gene Transcription that Relate to Behavioural Outcomes.

Synthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery to reduce respiratory distress syndrome in the newborn. The prefrontal cortex (PFC) is important in regulating stress responses and related behaviours and expresses high levels of glucocorticoid receptors (GR). Further, antenatal exposure to sGC results in a hyperactive phenotype in first generation (F) juvenile male and female offspring, as well as F and F juvenile females from the paternal lineage.

A Single Course of Synthetic Glucocorticoids in Pregnant Guinea Pigs Programs Behavior and Stress Response in Two Generations of Offspring.

Treatment with a single course of synthetic glucocorticoids (sGCs) is the standard of care for pregnant women who are at risk for preterm delivery. Animal studies have demonstrated that multiple course sGCs can program altered hypothalamic-pituitary-adrenal (HPA) axis response to stress in first-generation (F1) and second-generation (F2) offspring. In this study, we sought to determine whether HPA axis activity and stress-associated behaviors (i.

Prenatal Glucocorticoid Exposure Modifies Endocrine Function and Behaviour for 3 Generations Following Maternal and Paternal Transmission.

Fetal exposure to high levels of glucocorticoids programs long-term changes in the physiologic stress response and behaviours. However, it is not known whether effects manifest in subsequent generations of offspring following maternal (MT) or paternal (PT) transmission. We treated pregnant guinea pigs with three courses of saline or synthetic glucocorticoid (sGC) at a clinically relevant dose.

Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier.

Background/aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB).

Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding, DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus.

The endogenous glucocorticoid (GC) surge in late gestation plays a vital role in maturation of several organ systems. For this reason, pregnant women at risk of preterm labor are administered synthetic glucocorticoids (sGCs) to promote fetal lung development. Animal studies have shown that fetal sGC exposure can cause life-long changes in endocrine and metabolic function.

Glucocorticoid programming of the fetal male hippocampal epigenome.

The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring.

Prenatal synthetic glucocorticoid treatment changes DNA methylation states in male organ systems: multigenerational effects.

Prenatal synthetic glucocorticoids (sGC) are administered to pregnant women at risk of delivering preterm, approximately 10% of all pregnancies. Animal studies have demonstrated that offspring exposed to elevated glucocorticoids, either by administration of sGC or as a result of maternal stress, are at increased risk of developing behavioral, endocrine, and metabolic abnormalities. DNA methylation is a covalent modification of DNA that plays a critical role in long-lasting programming of gene expression.

Transgenerational effects of prenatal synthetic glucocorticoids on hypothalamic-pituitary-adrenal function.

Approximately 10% of pregnant women are at risk of preterm delivery and receive synthetic glucocorticoids (sGC) to promote fetal lung development. Studies have indicated that prenatal sGC therapy modifies hypothalamic-pituitary-adrenal (HPA) function in first-generation (F(1)) offspring. The objective of this study was to determine whether differences in HPA function and behavior are evident in the subsequent (F(2)) generation.