Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep.
In this study, we determined the effect of maternal undernutrition in the periconceptional (PCUN: ~80 days before to 6 days after conception) and preimplantation (PIUN: 0-6 days after conception) periods on the mRNA and protein abundance of key factors regulating myogenesis and protein synthesis, and on the relationship between the abundance of these factors and specific microRNA expression in the quadriceps muscle of singleton and twin fetal sheep at 135-138 days of gestation. PCUN and PIUN resulted in a decrease in the protein abundance of MYF5, a factor which determines the myogenic lineage, in singletons and twins. Interestingly, there was a concomitant increase in insulin-like growth factor-1 mRNA expression, a decrease in the protein abundance of the myogenic inhibitor, myostatin (MSTN), and an increase in the mRNA and protein abundance of the MSTN inhibitor, follistatin (FST), in the PCUN and PIUN groups in both singletons and twins. These promyogenic changes may compensate for the decrease in MYF5 protein abundance evoked by early embryonic undernutrition. PCUN and PIUN also increased the protein abundance of phosphorylated eukaryotic translation initiation factor binding protein 1 (EIF4EBP1; T70 and S65) in fetal muscle in singletons and twins. There was a significant inverse relationship between the expression of miR-30a-5p, miR-30d-5p, miR-27b-3p, miR106b-5p, and miR-376b and the protein abundance of mechanistic target of rapamycin (MTOR), FST, or MYF5 in singletons or twins. In particular, the expression of miR-30a-5p was increased and MYF5 protein abundance was decreased, in PCUN and PIUN twins supporting the conclusion that the impact of PCUN and PIUN is predominantly on the embryo.
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Shervi
S
Lie
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Janna L
http://orcid.org/0000-0002-8602-8519
JL
Morrison
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Olivia
O
Williams-Wyss
Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia.
Catherine M
CM
Suter
Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
David T
DT
Humphreys
Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Susan E
SE
Ozanne
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Song
S
Zhang
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Severence M
SM
MacLaughlin
South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, South Australia, Australia.
David O
DO
Kleemann
South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, South Australia, Australia.
Simon K
SK
Walker
Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, South Australia, Australia.
Claire T
CT
Roberts
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia The Chancellery, University of Newcastle, Newcastle, New South Wales, Australia caroline.mcmillen@newcastle.edu.au.
I Caroline
IC
McMillen
Embryo; fetus; nutrition; oocyte