Author
BORENGASSER, SARAH - Arkansas Children'S Nutrition Research Center (ACNC) | |
FASKE, JENNIFER - Arkansas Children'S Nutrition Research Center (ACNC) | |
KANG, PING - Arkansas Children'S Nutrition Research Center (ACNC) | |
ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC) | |
SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC) |
Submitted to: Diabetes
Publication Type: Abstract Only Publication Acceptance Date: 3/11/2013 Publication Date: 6/15/2014 Citation: Borengasser, S., Faske, J., Kang, P., Zhong, Y., Shankar, K. 2014. Maternal exercise is associated with transcriptomic adaptations in late gestation mouse placenta. Diabetes. 63(Supplement 1 - A170-A212):717-P. Interpretive Summary: Exercise leads to many beneficial health benefits. More recently, it has been reported that maternal exercise may lead to beneficial health in the offspring. However, little is known regarding the mechanisms that maternal exercise may alter during pregnancy. We hypothesized that maternal exercise prior to and during pregnancy will lead to changes in gene expression in the placenta and gender differences will be evident. We found that female mice provided access to voluntary running wheels did show differences in placenta gene transcripts as compared to mice that had no access to running wheels, remained sedentary. Moreover, there were apparent differences between male and female placentas due to maternal exercise. Exercise induced more changes in females than males, 661 versus 283 transcripts altered. In male placenta, maternal exercise led to enrichment of genes involved in neurotransmitter levels, glutamate signaling, and feeding behavior while decreasing lipid biosynthetic process and lipid transport. Maternal exercise in female placenta led to increases in gene involved in skeletal muscle, heart, and brain development and decreases in hormone metabolic process and apoptosis. Importantly, we identified 28 transcripts that were affected uniformly by maternal exercise in both males and females which primarily were associated with functions in brain development. We confirmed our transcript findings by measuring mRNA expression of key targets. For example, Cathepsin C, tryptophan hydroxylase, RARRES1, CIDE C, Acox2, and Slc27a2 were all decreased by maternal exercise and low-density lipoprotein receptor 1 was increased in both male and female placenta, suggesting changes in brain development and energy metabolism. Our results suggest that maternal exercise induces changes in the placenta that may evoke neuronal- and metabolic-related benefits in offspring health. Technical Abstract: Exercise (EX) induces pleiotropic health benefits. Recent studies indicate beneficial effects of maternal (mat) EX on offspring health; however, little is known about the mechanisms by which mat EX mediates changes in utero. We hypothesized that effects of mat EX prior to and during gestation will be evident in transcriptomic signatures in the placenta and will be sexually dimorphic. Six wk old female C57BL/6 mice were divided into 2 groups; with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24-h access to wheels for 10 wk prior to conception until the end of the study (18.5 days post coitum). At sacrifice mat tissues and placenta were collected from individual pups and sex-identified via PCR for the Sry gene. Microarray analysis of SED and EX placenta (GeneChip 430 2.0) revealed that EX affected expression of 283 and 661 transcripts in male and female placenta (± 1.4-fold, p < 0.05). Gene-set enrichment analysis showed that EX in male placenta led to enrichment of genes involved in neurotransmitter levels, glutamate signaling, and feeding behavior while decreasing lipid biosynthetic process and lipid transport. EX in female placenta led to increases in genes involved in skeletal muscle, heart, and brain development and decreases in hormone metabolic process and apoptosis. Importantly, we identified 28 transcripts that were affected uniformly by EX in both sexes, which primarily encompassed functions in brain development. Using qPCR, we confirmed mRNA expression of Cathepsin C, tryptophan hydroxylase, RARRES1, CIDE C, Acox2, and Slc27a2 were reduced by EX (p < 0.05) and low-density lipoprotein receptor 1 was increased (p < 0.05) in both male and female placenta, suggesting changes in brain development and energy metabolism. Our results suggest that mat EX induces placental alterations that may evoke neuronal- and metabolic-related benefits in offspring health. |