Moderate Exercise during Pregnancy in Wistar Rats Alters Bone and Body Composition of the Adult Offspring in a Sex-Dependent Manner

Abstract

Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively). At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01) and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02); however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during pregnancy can result in lasting changes to the musculoskeletal system and adiposity in offspring, in a sex-specific manner.

Homage to the ‘H’ in developmental origins of health and disease

“…37 Long lasting changes in the musculoskeletal system and adiposity are observed in Wistar rat offspring, especially in males, of exercised dams. 38 Such changes include lower bone mineral density, increase circulating concentrations of undercarboxylated osteocalcin and greater percentage of total fat but lower percentage of lean fat compared with controls. The beneficial metabolic effects in offspring of exercised dams may be due to gene expression changes in skeletal muscle, such as decrease Il6 (an inflammatory cytokine secreted by T-lymphocytes and macrophages), 39 increase peptide Pyy (a peptide released from the ileum and colon in response to feeding), 39 and decrease hypermethylation/increased expression of Pgc1a (a transcriptional co-activator regulating many genes involved in energy metabolism).…”

“…However, male offspring from exercised, obese dams showed reduced glucose concentrations Maternal exercise did not impact blood glucose concentrations in female pups Insulin concentrations were reduced in male pups from exercised lean and obese dams Female pups from obese, non-exercised dams were significantly increased, and maternal exercise did not alter insulin concentrations in female offspring Plasma triglycerides were lower in male pups from lean exercised dams but increased in those from obese exercised dams Glut4 (glucose transporter) and Myod1 (moygenesis-related gene) was downregulated in male offspring from non-exercised, obese dams but normalized in those from exercised, obese dams. Pgc1α, a transcriptional co-activator regulating many genes involved in energy metabolism, was upregulated in male offspring from exercised dams Glut4 and Pgc1a were upregulated in retroperitoneal white adipose tissue (WAT) of male and female offspring from lean but not obese exercised dams Tnf-α (a marker of inflammation) was elevated in male pups from both lean and obese exercised dams but in females, this gene was only increased in lean exercised dams Il6, another inflammatory marker, was elevated in male pups from lean and to a lesser extent obese exercised dams 37 Female Sprague Dawley rats Maternal exercise (voluntary wheel running) before mating and throughout pregnancy and lactation Female offspring of exercised dams displayed enhanced glucose turnover during glucose tolerance testing, increased glucose infusion rates, and whole body glucose turnover rates during hyperinsulinemic-euglycemic clamp testing Female offspring from exercised dams had decreased insulin levels and hepatic glucose production during the clamp procedure Insulin infusion resulted in increased glucose uptake in skeletal muscle and decreased heart glucose uptake in offspring of exercised dams 38 Male and female Wistar Albino rats Maternal exercise before mating and throughout gestation for control and obese dams Serum corticosterone was increased in neonatal offspring of non-exercised obese dams but decreased in offspring from exercised control and obese dams Insulin was increased in male offspring of non-exercised obese dams Leptin and triglycerides were increased in male offspring of obese non-exercised dams but leptin and partially triglycerides were reduced in those from obese exercised dams Glucose and homeostasis model assessment (HOMA), calculated from HOMA = glucose (mmol/l) × insulin (μU/ml), were decreased in male and female offspring of control exercised dams 39 Male and female Wistar rats Maternal exercise 5 days before breeding and throughout pregnancy…”

Pregnancy, Exercise and Late Effects in the Offspring until Adult Age

“…Alter bone and adiposity in a gender-specific way [39]. The positive effects of preconceptual training comparing groups of female mice with or without voluntary Ex in running wheels were revealed in significant changes of bone gene expressions, in particular towards osteogenic remodelling markers [40].…”

53: Is Caffeine a Risk Factor for Osteopenia of Prematurity?

“…In a study which tested the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring, the results suggest that moderate exercise during pregnancy can result in lasting changes to the musculoskeletal system and adiposity in offspring (Rosa, Blair & Vickers, 2013).…”