Cerebrum, liver, and muscle regulatory networks uncover maternal nutrition effects in developmental programming of beef cattle during early pregnancy

Authors: DINIZ, WELLISON - North Dakota State University; Crouse, Matthew; Cushman, Robert - Bob; MCLEAN, KYLE - University Of Tennessee; CATON, JOEL - North Dakota State University; DAHLEN, CARL - North Dakota State University; REYNOLDS, LAWRENCE - North Dakota State University; WARD, ALISON - North Dakota State University

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2021
Publication Date: 2/2/2021
Citation: Diniz, W.J., Crouse, M.S., Cushman, R.A., McLean, K.J., Caton, J.S., Dahlen, C.R., Reynolds, L.P., Ward, A.K. 2021. Cerebrum, liver, and muscle regulatory networks uncover maternal nutrition effects in developmental programming of beef cattle during early pregnancy. Scientific Reports. 11. Article 2771. https://doi.org/10.1038/s41598-021-82156-w.
DOI: https://doi.org/10.1038/s41598-021-82156-w

Interpretive Summary: Previous research produced by our lab group has shown that a moderate maternal nutrient restriction during the first 50 days of gestation altered transcript abundance of genes related to fetal tissue accretion, metabolism, and function. Furthermore, these data showed that 78% of altered transcripts were increased in offspring of restricted vs. control mothers. These data resulted in interpretation that offspring may be either compensating for decreased nutrient availability and would therefore undergo compensatory growth when re-fed, or that the increase in transcript abundance was negatively regulating growth. This study built upon these data using regulatory gene co-expression networks to determine if the changes in transcript abundance we previously reported were negatively or positively impacting fetal development. This analysis shows that maternal nutrient restriction alters regulators of gene targets that may negatively affect myogenesis, and nutrient sensing pathways. These results unveiled the network properties of gene regulation due to maternal nutrient restriction in beef cattle and helped to gain systems level insights into fetal programming.

Technical Abstract: The molecular basis underlying fetal programming in response to maternal nutrition remains unclear. Herein, we investigated the regulatory relationships between genes in fetal cerebrum, liver, and muscle tissues to shed light on the putative mechanisms underlying the effects of early maternal nutrient restriction on bovine developmental programming. To this end, cerebrum, liver, and muscle gene expression were measured with RNA-Seq in 14 fetuses collected on day 50 of gestation from dams fed a diet initiated at breeding to either achieve 60% (RES, n = 7) or 100% (CON, n = 7) of energy requirements. To build a tissue-to-tissue gene network, we prioritized tissue-specific genes, transcription factors, and differentially expressed genes. Furthermore, we built condition-specific networks to identify differentially co-expressed or connected genes. Nutrient restriction led to differential tissue regulation between the treatments. Myogenic factors differentially regulated by ZBTB33 and ZNF131 may negatively affect myogenesis. Additionally, nutrient-sensing pathways, such as mTOR and PI3K/Akt, were affected by gene expression changes in response to nutrient restriction. By unveiling the network properties, we identified major regulators driving gene expression. However, further research is still needed to determine the impact of early maternal nutrition and strategic supplementation on pre- and post-natal performance.