title: Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat.
abstract: Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC)in uteroimpairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are unknown. To test the hypothesis that blunting of Pax7+ muscle progenitor cell proliferative activity by GLCin vivoalso contributes to reduced fetal muscle growth, pregnant rats were administered dexamethasone (DEX: 1 mg/L drinking water) from embryonic day (ED) 13 to ED21. Their responses were compared to pair-fed (PF) andad libitum-fed controls (CON). Bromodeoxyuridine (BrdU) was administered before delivery to measure myonuclear accretion. Fetal hind limb and diaphragm muscles were collected at term and analyzed for myofiber cross-sectional area (CSA), total and BrdU+ myonuclei, Pax7+ nuclei, MyoD and myogenin protein and mRNA abundance and myosin heavy chain (MyHC) isoform composition. Mean fiber CSA, myonuclei/myofiber and Pax7+ nuclei/myofiber ratios were reduced in DEX compared to those in CON and PF muscles; CSA/myonucleus, BrdU+/total myonuclei and BrdU+ myonuclei/Pax7+ nuclei were similar among groups. Myogenin abundance was reduced and MyHC-slow was increased in DEX fetuses. The data are consistent with GLC inhibition of muscle progenitor cell proliferation limiting satellite cell and myonuclear accretion. The response of PF-fed compared to CON muscles indicated that decreased food consumption by DEX dams contributed to the smaller myofiber CSA but did not affect Pax7+ nuclear accretion. Thus, the effect on satellite cell reserve and myonuclear number also contributes to the blunting of fetal muscle growth by GLC.
authors.affiliation: USDA/ARS Children's Nutrition Research CenterDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.|Department of PediatricsTexas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ganga
authors.initials: G
authors.lastname: Gokulakrishnan
authors.affiliation: USDA/ARS Children's Nutrition Research CenterDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chang
authors.affiliation: USDA/ARS Children's Nutrition Research CenterDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: USDA/ARS Children's Nutrition Research CenterDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA martaf@bcm.edu.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D018008:Myogenin; C530821:PAX7 protein, rat; D051761:Paired Box Transcription Factors; D003907:Dexamethasone; D018995:Myosin Heavy Chains
keywords: food restriction; hypertrophy; muscle regulatory factors; myosin; skeletal muscle