ABSTRACT
Antenatal administration of glucocorticoids such as betamethasone (BMZ) during the late preterm period improves neonatal respiratory outcomes. However, glucocorticoids may elicit programming effects on immune function and gene regulation. Here, we test the hypothesis that exposure to antenatal BMZ alters cord blood immune cell composition in association with altered DNA methylation and alternatively expressed Exon 1 transcripts of the glucocorticoid receptor (GR) gene in cord blood CD4+ T-cells. Cord blood was collected from 51 subjects in the Antenatal Late Preterm Steroids Trial: 27 BMZ, 24 placebo. Proportions of leukocytes were compared between BMZ and placebo. In CD4+ T-cells, methylation at CpG sites in the GR promoter regions and expression of GR mRNA exon 1 variants were compared between BMZ and placebo. BMZ was associated with an increase in granulocytes (51.6% vs. 44.7% p = 0.03) and a decrease in lymphocytes (36.8% vs. 43.0% p = 0.04) as a percent of the leukocyte population vs. placebo. Neither GR methylation nor exon 1 transcript levels differed between groups. BMZ is associated with altered cord blood leukocyte proportions, although no associated alterations in GR methylation were observed.
Subject(s)
Glucocorticoids , Premature Birth , Betamethasone , DNA Methylation , Exons , Female , Fetal Blood/metabolism , Glucocorticoids/pharmacology , Humans , Infant, Newborn , Pregnancy , Premature Birth/metabolism , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolismABSTRACT
Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.
Subject(s)
Cholesterol/metabolism , Diet, High-Fat , Fetal Growth Retardation/metabolism , Liver/metabolism , Prenatal Exposure Delayed Effects , Receptors, LDL/metabolism , Age Factors , Animal Nutritional Physiological Phenomena , Animals , Disease Models, Animal , Female , Fetal Growth Retardation/physiopathology , Lactation , Male , Maternal Nutritional Physiological Phenomena , Pregnancy , Rats, Sprague-Dawley , Up-RegulationABSTRACT
Obese women are at increased risk for multiple labor abnormalities, including postdates pregnancy, failed induction of labor, prolonged labor, cesarean delivery, and postpartum hemorrhage (PPH). Prolonged labor among obese women is confined to the first stage of labor. In the setting of reassuring fetal and maternal status, increased time to progress in the first stage of labor should be allowed. Uterine atony occurs more frequently in obese women and vigilance in the prevention of PPH is critical. There is a lack of high-quality data to guide the management of induction, labor, and PPH prevention among obese women.
