PMID- 32222553 OWN - NLM STAT- MEDLINE DCOM- 20210724 LR - 20240229 IS - 1879-0054 (Electronic) IS - 0739-7240 (Linking) VI - 72 DP - 2020 Jul TI - Effect of maternal nutrient restriction on skeletal muscle mass and associated molecular pathways in SGA and Non-SGA sheep fetuses. PG - 106443 LID - S0739-7240(20)30010-2 [pii] LID - 10.1016/j.domaniend.2020.106443 [doi] AB - Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Sandoval, C AU - Sandoval C AD - Department of Animal Science, Texas A&M University, College Station, TX 77843, USA. FAU - Lambo, C A AU - Lambo CA AD - Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, TX 77843, USA. FAU - Beason, K AU - Beason K AD - Department of Animal Science, Texas A&M University, College Station, TX 77843, USA. FAU - Dunlap, K A AU - Dunlap KA AD - Department of Animal Science, Texas A&M University, College Station, TX 77843, USA. FAU - Satterfield, M C AU - Satterfield MC AD - Department of Animal Science, Texas A&M University, College Station, TX 77843, USA. Electronic address: csatterfield@tamu.edu. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200217 PL - United States TA - Domest Anim Endocrinol JT - Domestic animal endocrinology JID - 8505191 SB - IM MH - Animals MH - Female MH - Pregnancy MH - *Animal Feed/analysis MH - Animal Nutritional Physiological Phenomena MH - Diet/veterinary MH - *Fetal Development MH - *Food Deprivation MH - Gestational Age MH - *Muscle, Skeletal/growth & development MH - Prenatal Nutritional Physiological Phenomena MH - *Sheep/growth & development OTO - NOTNLM OT - Hypertrophy OT - Maternal nutrient restriction OT - SGA OT - Skeletal muscle OT - Spectral phenotype EDAT- 2020/03/31 06:00 MHDA- 2021/07/24 06:00 CRDT- 2020/03/31 06:00 PHST- 2019/09/06 00:00 [received] PHST- 2020/01/14 00:00 [revised] PHST- 2020/01/22 00:00 [accepted] PHST- 2020/03/31 06:00 [pubmed] PHST- 2021/07/24 06:00 [medline] PHST- 2020/03/31 06:00 [entrez] AID - S0739-7240(20)30010-2 [pii] AID - 10.1016/j.domaniend.2020.106443 [doi] PST - ppublish SO - Domest Anim Endocrinol. 2020 Jul;72:106443. doi: 10.1016/j.domaniend.2020.106443. Epub 2020 Feb 17.