Cross-fostering selectively bred High Runner mice affects adult body mass but not voluntary exercise

• Published in: Physiology & behavior Vol. 241; p. 113569
• Main Authors: Cadney, Marcell D., Schwartz, Nicole E., McNamara, Monica P., Schmill, Margaret P., Castro, Alberto A., Hillis, David A., Garland, Theodore
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2021
• Subjects: adulthood; adults; Behavior; Body composition; body weight; Cross-fostering; exercise; Exercise physiology; Indirect genetic effect; maternal behavior; Maternal effect; musculoskeletal system; peak oxygen uptake; phenotype; progeny; Rodents; Exercise physiology; Indirect genetic effect; Cross-fostering; Rodents; Behavior; Maternal effect; Body composition
• ISSN: 0031-9384; 1873-507X; 1873-507X
• DOI: 10.1016/j.physbeh.2021.113569

•Lines of High Runner mice were selectively bred for voluntary wheel activity.•Cross-fostering was used to test for early postnatal maternal effects.•Mice fostered to High Runner dams had reduced body mass.•Cross-fostering had numerous sex-specific effects on adult phenotypes.•Adult voluntary wheel-running behavior was unaffected by cross-fostering. While nursing, mammals progress through critical developmental periods for the cardiovascular, musculoskeletal, and central nervous systems. The suckling period in mammals is therefore especially vulnerable to environmental factors that may affect the “developmental programming” of many complex traits. As a result, various aspects of maternal behavior and physiology can influence offspring in ways that have lasting effects into adulthood. Several recent studies of animal models have shown that maternal effects can partially program adult activity behaviors, which has important implications for health and locomotor performance. Here, we used cross-fostering to test for possible maternal effects on adult wheel-running behavior (voluntary exercise), maximal aerobic capacity during forced exercise (VO2max), body mass and composition, and organ masses. Subjects were from a line of mice that has been selectively bred for ∼90 generations for high voluntary wheel-running behavior (High Runner; HR) and a non-selected Control (C) line. Adult HR mice run ∼3-fold the daily distances of C mice and have evolved other differences associated with exercise capacity, including elevated VO2max, reduced body mass and fat mass, and larger hearts. At birth, we fostered offspring to create 4 experimental groups: C pups to other C dams (in-foster), HR pups to other HR dams (in-foster), C pups to HR dams (cross-foster), HR pups to C dams (cross-foster). Thus, all pups were fostered to a different mother. Mice were weaned 3 weeks later, and adult testing began at ∼6 weeks of age. At weaning, pups raised by HR dams were smaller than those raised by C dams for both sexes and as expected, HR pups raised by HR dams weighed less than C pups raised by C dams. As adults, mice raised by HR dams continued to have reduced body masses. As expected, adult HR mice ran approximately 3-fold more than their C counterparts and females ran more than males. However, cross-fostering did not statistically affect any aspect of wheel-running behavior (distance, duration, speed). Similarly, with body mass as a covariate, HR mice had higher VO2max than C mice, and males had higher VO2max than females, but cross-fostering had no effect. With body mass as a covariate, cross-fostering had variable effects on adult organ masses in a sex-specific manner. Overall, our results indicate that development of the adult High Runner phenotype does not require rearing by an HR dam, suggesting that high adult activity in humans may be independent of high maternal activity.