Sex‐specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring

Abstract

Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or “exercise ancestry,” on morphological and metabolic phenotypes in two generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bred with like-exposed mates to produce an F1 generation. F1 mice of both ancestries were sedentary and sacrificed at 8 wk or bred with littermates to produce an F2 generation, which was also sedentary and sacrificed at 8 wk. Small, but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance, and muscle gene expression. F1 EX females were lighter than F1 SED females, and had lower absolute tibialis anterior and omental fat masses. Serum insulin was higher in F1 EX females compared to F1 SED females. F2 EX females had impaired glucose tolerance compared to F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g., F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1α, Adipoq, and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring.

Impact of Maternal Exercise during Pregnancy on Offspring Chronic Disease Susceptibility

“…A recent report examined the effects of exercise ancestry on metabolic phenotypes in multiple generations of mouse offspring (16). The F0 generation mothers exercised during pregnancy producing the F1 generation.…”

“…The F0 generation mothers exercised during pregnancy producing the F1 generation. Breeding of the F1 generation produced F2 offspring with either a sedentary or exercise ancestry (16). Glucose tolerance test results indicated that only the female F2 generation offspring were affected, with those offspring from an exercise ancestry displaying impaired glucose tolerance compared to their sedentary counterpart (16).…”

“…Glucose tolerance test results indicated that only the female F2 generation offspring were affected, with those offspring from an exercise ancestry displaying impaired glucose tolerance compared to their sedentary counterpart (16). While these data do not fall in line with previous reports (7, 8), it is important to note that the mouse offspring from Guth et al (16) were only 8 weeks old at the time of testing, whereas the offspring from other studies were 31–32 weeks (7) or 10 months of age (8). This discrepancy in whether or not maternal exercise during pregnancy produces an improved glucose profile in the offspring points to a further need to examine offspring at varying ages and under additional metabolic stressors.…”

The role of diet and exercise in the transgenerational epigenetic landscape of T2DM

“…Nevertheless, little is known about the mechanism by which exercise effects various metabolic phenotypes over several generations. One study compared and contrasted the effects of maternal and paternal exercise training in rodents on anatomical and metabolic characteristics, including gene expression in skeletal muscle, to that of their sedentary offspring over two generations 60 . Exercise training resulted in sex-dependent metabolic improvements, as demonstrated by reduced body weight and fat mass in male offspring and increased skeletal muscle mass and improved glucose tolerance in female offspring.…”

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

“…Small, but broad generation-and sexspecific effects of Ex ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance and muscle gene expression (mRNA levels for multiple genes, especially those related to metabolic genes), which varied with regard to first and second generation of mice followed up [42].…”