Effects of maternal and paternal exercise on offspring metabolism

Abstract

Maternal and paternal obesity and type 2 diabetes are recognized risk factors for the development of metabolic dysfunction in offspring, even when the offspring follow a healthful lifestyle. Multiple studies have demonstrated that regular physical activity in mothers and fathers has striking beneficial effects on offspring health, including preventing the development of metabolic disease in rodent offspring as they age. Here, we review the benefits of maternal and paternal exercise in combating the development of metabolic dysfunction in adult offspring, focusing on offspring glucose homeostasis and adaptations to metabolic tissues. We discuss recent findings regarding the roles of the placenta and sperm in mediating the effects of parental exercise on offspring metabolic health, as well as the mechanisms hypothesized to underlie these beneficial changes. Given the worldwide epidemics of obesity and type 2 diabetes, if these findings translate to humans, regular exercise during the reproductive years might limit the vicious cycles in which increased metabolic risk propagates across generations.

Fig 1:. Intergenerational Effects of Environmental Exposure.

In females, intergenerational transmission occurs when a dam receives an environmental exposure during pregnancy, affecting not only F0, but also the F1 and F2 generations. Exposures during pregnancy can directly affect the embryo and its progenitor germs cells. During F1 maturation, these germ cells will become the adult gametes that create the F2 generation.

Fig 2:. Parental Exercise Training Affects Parents and Offspring.

When women exercise before pregnancy, their oocytes may be affected and exercise during pregnancy affects placenta. These alterations result in numerous effects in the F1 newborn, adaptations that may continue into adulthood. When men are exposed to exercise before breeding, their sperm physiology is changed which may lead to changes in F1 as newborns. Whether these changes affect health of the offspring as they age to adulthood is not known. More studies are needed to understand the effects of maternal and paternal exercise on offspring health in adulthood and to determine mechanisms for these effects.

Fig. 3:. Targets and Timing of Parental Exercise Differently Affect Offspring Through Inter- or Trans-generational Modes of Inheritance.

A. Inter-generational effects of maternal exercise during pregnancy on F1 and F2 offspring. F0 exercise directly affects the F1 fetus and F2 germ progenitor cells present in the F0 womb. B. Trans-generational effects of maternal exercise during pregnancy on F2 offspring. F0 exercise indirectly affects the development of the F2 fetus through F0-induced changes to F1 metabolic phenotypes, which subsequently influence the F2 generation. C. Inter-generational effects of maternal exercise while non-pregnant on F1 offspring. F0 exercise directly affects maternal oocytes, altering the F1 phenotype. D. Inter-generational effects of paternal exercise on F1 offspring. F0 exercise directly affects the paternal sperm, altering the F1 phenotype. E. Trans-generational effects of paternal exercise on F2 offspring. F0 exercise indirectly affects the development of the F2 fetus through F0-induced metabolic changes to F1 males (F1 phenotype affecting spermatogenesis) or females (F1 phenotype affecting oogenesis or the intrauterine environment).

Fig 4:. Effects of Maternal and Paternal Exercise Training on F1 Offspring Metabolism.

Maternal exercise improves numerous aspects of offspring metabolism. Whether maternal exercise effects F2 offspring is not known. Most studies show that when sires are exposed to exercise before breeding, F1 offspring have improved metabolism.

Fig 5:. Effects of Exercise Training in Rodents on F0 Gametes and Placenta, and on F1 Newborn and Adults.

When dams are exposed to exercise before and during pregnancy, their oocytes and placenta are affected. While litter size and pup weight are generally not affected by maternal exercise, there are numerous beneficial metabolic changes in offspring, most prevalent in adulthood. Sires that are exposed to exercise have numerous alterations in sperm and these changes likely mediate the beneficial metabolic changes in F1 offspring. There are some sex-specific adaptations in the offspring in response to both maternal and paternal exercise. The beneficial effects of parental exercise offspring may be propagated across subsequent generations, ensuring healthier life cycles for further progeny.