Available online 11 March 2024, 101914

Maternal exercise prevents the detrimental effects of maternal HFD on female offspring cardiovascular health in vivo (LVEF) and improves cardiomyocyte function in vitro.

The improvements in cardiomyocyte shortening and calcium cycling are the result of preserved mitochondrial function and RyR2 activity (reduced RyR2 oxidation and SR calcium leak).

These data are the first to identify a potential mechanism for maternal exercise to mediate adult offspring cardiovascular health via oxidative regulation of RyR2 by mito-ROS, and highlight the profound effects of the maternal environment on the life-long cardiac health of offspring.

The intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated.

To determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 24 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies.

High-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 24 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring.

These data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.

maternal

offspring

cardiac

cardiovascular

RyR2

calcium

mitochondria

mitoROS

respiration

Calcium-induced calcium-release

Offspring from chow-fed, sedentary dams

Carbonyl cyanide-p-trifluoromethoxy-phenyl-hydrazon

Offspring from high fat diet-fed, sedentary dams

Offspring from high fat diet-fed, wheel exercised dams

Left-ventricle diastolic diameter

Left-ventricle ejection fraction

Mitochondrial reactive oxygen species

Sodium-calcium exchanger

Oxygen consumption rate

Ryanodine receptor type 2

Sarco-Endoplasmic reticulum Ca2+ ATPase type 2a

© 2024 The Author(s). Published by Elsevier GmbH.