PMID- 36839409 OWN - NLM STAT- MEDLINE DCOM- 20230228 LR - 20230301 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 15 IP - 4 DP - 2023 Feb 20 TI - Multi-Omics Analysis Reveals the Potential Effects of Maternal Dietary Restriction on Fetal Muscle Growth and Development. LID - 10.3390/nu15041051 [doi] LID - 1051 AB - In terms of fetal muscle growth, development, and health, maternal nutrition is a crucial influence, although the exact biochemical mechanism by which this occurs is still not fully understood. To examine the potential impacts of maternal dietary restriction on fetal muscle development, the sheep maternal dietary restriction model was developed for this study. In our study, 12 pregnant ewes were evenly split into two experimental groups and fed either 75% or 100% of a maternal nutrient. In addition, a multi-omics analysis was used to study the embryonic longissimus dorsis on gestational days (GD) 85 and 135. The fetal weight at GD 135 was significantly below normal due to the maternal restricted diet (p < 0.01). When fetuses were exposed to the dietary deficit, 416 mRNAs and 40 proteins were significantly changed. At GD 85, the multi-omics analysis revealed that maternal dietary restriction led to a significant up-regulation of the cell cycle regulator CDK2 gene in the cellular senescence signaling pathway, and the results of the qRT-PCR were similar to the multi-omics analysis, which showed that SIX1, PAX7, the cell cycle factors CDK4 and CDK6, and the BCL-2 apoptosis factor were up-regulated and several skeletal muscle marker genes, such as MYF5 and MyoD were down-regulated. At GD 135, maternal dietary restriction blocks the muscle fiber differentiation and maturation. The multi-omics analysis revealed that the TEAD1 gene was in the Hippo signaling pathway, the muscle marker genes MYF5 and MyoG were significantly down-regulated, and the TEAD1 binding of the down-regulated VGLL3 gene might be potential mechanisms affecting myofiber differentiation and maturation. Knocking down the CDK2 gene could inhibit the proliferation of primary embryonic myoblasts, and the expression levels of cell cycle regulatory factors CDK4 and CDK6 were significantly changed. Under low nutrient culture conditions, the number of myoblasts decreased and the expression of CDK2, CDK6, MYF5, PAX7 and BCL-2 changed, which was in perfect agreement with the multi-omics analysis. All of the findings from our study helped to clarify the potential effects of maternal dietary restriction on fetal muscle growth and development. They also provided a molecular foundation for understanding the molecular regulatory mechanisms of maternal nutrition on fetal muscle growth and development, as well as for the development of new medications and the management of related metabolic diseases. FAU - Wang, Xinyue AU - Wang X AUID- ORCID: 0000-0002-8025-1760 AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. FAU - Shang, Mingyu AU - Shang M AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. FAU - Hu, Wenping AU - Hu W AUID- ORCID: 0000-0002-8962-7541 AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. FAU - Zhang, Li AU - Zhang L AUID- ORCID: 0000-0002-1197-843X AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. LA - eng GR - 2020ZD0003/Inner Mongolia Sciences & Technology Plan/ GR - 2021YFD1300902/national natural science fund joint fund key project: National Key R&D Program of China/ GR - 2018-YF-06 and 2018-YF-09/University-Enterprise Cooperative R&D Project "Research, Development and Application of Genome-Wide Selective Breeding Technology for Hu Sheep"/ PT - Journal Article DEP - 20230220 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM MH - Pregnancy MH - Animals MH - Female MH - Sheep MH - *Multiomics MH - *Fetal Development MH - Diet/veterinary MH - Muscle, Skeletal MH - Proto-Oncogene Proteins c-bcl-2 MH - Muscle Development PMC - PMC9964303 OTO - NOTNLM OT - fetal muscle OT - maternal dietary restriction OT - multi-omics analysis OT - proteome OT - sheep pregnancy model OT - transcriptome COIS- The authors have no competing interests. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/20 CRDT- 2023/02/25 04:10 PHST- 2023/01/30 00:00 [received] PHST- 2023/02/15 00:00 [revised] PHST- 2023/02/16 00:00 [accepted] PHST- 2023/02/25 04:10 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/20 00:00 [pmc-release] AID - nu15041051 [pii] AID - nutrients-15-01051 [pii] AID - 10.3390/nu15041051 [doi] PST - epublish SO - Nutrients. 2023 Feb 20;15(4):1051. doi: 10.3390/nu15041051.