Maternal exercise prior to and during gestation induces sex-specific alterations in the mouse placenta

Authors: Ruebel, Meghan; BORENGASSER, SARAH - University Of Oklahoma Health Sciences Center; ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC); KANG, PING - Arkansas Children'S Nutrition Research Center (ACNC); FASKE, JENNIFER - Arkansas Children'S Nutrition Research Center (ACNC); SHANKAR, KARTIK - University Of Colorado

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/2023
Publication Date: 11/17/2023
Citation: Ruebel, M., Borengasser, S.J., Zhong, Y., Kang, P., Faske, J., Shankar, K. 2023. Maternal exercise prior to and during gestation induces sex-specific alterations in the mouse placenta. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms242216441.
DOI: https://doi.org/10.3390/ijms242216441

Interpretive Summary: Exercise during pregnancy has been shown to be beneficial to both mother and child health, however the way by which exercise of mother is mediating these changes during pregnancy is not well understood. The goal of this research was to understand how exercise/physical activity prior to and during pregnancy affects the gene expression patterns of the placenta at late pregnancy. In this study, researchers used a mouse model where females were given access to a running wheel to exercise or no running wheel for 10 weeks before conception and throughout pregnancy. Then at late pregnancy (days post coitum 18.5 in the mouse) researchers collected individual placentas, fetal tails and fetal livers. Fetal tails were genotype to determine the sex of the individual placenta and fetal liver tissue. The investigators found effects of exercise prior to and during pregnancy affect the placenta in different ways depending if the fetus was male or female. Male placenta showed that maternal exercise led to inhibition of signaling pathways, biological functions, and down regulation of transcripts related to lipid and steroid metabolism, while maternal exercise in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that effects of maternal exercise/physical activity on the placenta and presumably on the offspring are influenced by maternal health status and sex of the baby.

Technical Abstract: While exercise (EX) is beneficial during pregnancy for both mother and child, little is known about the mechanisms by which maternal (MAT EX) mediates changes in utero. Six-week-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-hour access to wheels for 10 weeks prior to conception until late pregnancy (18.5 days post coitum). Sex-stratified placenta and fetal livers were collected. Microarray analysis of SED and EX placenta revealed that MAT EX affected gene transcript expression of 283 and 661 transcripts in male and female placenta (±1.4-fold, p < 0.05). Gene-set enrichment and Ingenuity Pathway analyses of male placenta showed that MAT EX led to inhibition of signaling pathways, biological functions, and down regulation of transcripts related to lipid and steroid metabolism, while MAT EX in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that effects of MAT EX on the placenta and presumably on the offspring are influenced by maternal habitus and are sexually dimorphic.