ABSTRACT
Antenatal administration of synthetic glucocorticoids (sGC) is the standard of care for women at risk for preterm labor before 34 gestational weeks. Despite their widespread use, the type of sGC used and their dose or the dosing regimens are not standardized in the United States of America or worldwide. Several studies have identified neural deficits and the increased risk for cognitive and psychiatric disease later in life for children administered sGC prenatally. However, the precise molecular and cellular targets of GC action in the developing brain remain largely undefined. In this study, we demonstrate that a single dose of glucocorticoid during mid-gestation in mice leads to enhanced proliferation in select cerebral cortical neural stem/progenitor cell populations. These alterations are mediated by dose-dependent changes in the expression of cell cycle inhibitors and in genes that promote cell cycle re-entry. This leads to changes in neuronal number and density in the cerebral cortex at birth, coupled to long-term alterations in neurite complexity in the prefrontal cortex and hippocampus in adolescents, and changes in anxiety and depressive-like behaviors in adults.
Subject(s)
Behavior, Animal/drug effects , Cerebral Cortex/drug effects , Dexamethasone/pharmacology , Neural Stem Cells/drug effects , Neurons/drug effects , Prenatal Exposure Delayed Effects/pathology , Animals , Anxiety/pathology , Anxiety/psychology , Cell Count , Cell Shape/drug effects , Cerebral Cortex/pathology , Depression/pathology , Depression/psychology , Female , Hippocampus/drug effects , Hippocampus/pathology , Mice , Neural Stem Cells/pathology , Neurons/pathology , Pregnancy , Prenatal Exposure Delayed Effects/psychologyABSTRACT
Two hundred ninety-six gestating sows were used to determine the physical dimensions of sows in commercial settings. Sows were examined from five farms within a single production model that included identical feed formulation, management practices, herd health, and similar, but not identical, genotypes. Sows were individually weighed, backfat thickness was determined by ultrasound, and body dimensions were determined. Sow body length, height, width (lateral length, left to right from mid-line), and depth (measured as distance from ventral to dorsal extremes) were also determined. Regression procedures were used to model the changes in sow body size in relation to parity, BW, and stage of gestation within and among genotypes. Farm-to-farm variation in sow dimensions for the same genotype was also determined. Least squares means, SD, and 95% upper confidence limits of this sample are presented. Sows increased (P < 0.001) in body dimensions by predicable levels with parity (r2 = 0.92) up to Parity 6, and with advancing pregnancy (r2 = 0.99). Sows of different but related genotypes differed (P < 0.01) in body length, width, height, and depth. Sows of the same genotype, fed the same feed formulation, differed in body dimensions when managed on different farms. Based on mean values and a 95% confidence interval, stall width would need to be at least 72.4 cm to accommodate all sows on the farm. These data and models can be used to design stall sizes and farm floor space needs to meet current animal welfare recommendations. To accommodate the body size of pregnant sows on commercial farms, stall sizes for the majority of sows would need to increase, as would the total floor space needed for a given number of gestating sows individually penned in conventional production systems to meet recently published guidelines.