Journal Article

Impact of diet and exercise in growth restricted female rats on nephron endowment in male fetuses

Mangwiro, Yeukai T. M., Mahizir, Dayana, Charchar, Fadi, Moritz, Karen M., Gravina, Sogand, Wlodek, Mary E., Briffa, Jessica F., Anevska, Kristina, Richter, Viktoria F., Wadley, Glenn D., Hryciw, Deanne H., Cuffe, James S. M.

2026

Overview

Uteroplacental insufficiency impairs kidney development and programs male‐onset cardiorenal disease, which can be transmitted to subsequent generations. Maternal lifestyle factors can independently influence fetal kidney development, highlighting that the lifestyle of growth‐restricted females can have further influence on F2 kidney development. In this study, we examined the impact of maternal growth restriction with or without additional lifestyle factors on F2 male kidney development. Uteroplacental insufficiency (Restricted) or sham (Control) surgery was performed on embryonic day 18 in Wistar–Kyoto rats. F1 females were fed a Chow or High‐fat diet from weaning (5 weeks of age). At 16 weeks, females were randomly allocated to an exercise group: no exercise (Sedentary); exercised prior to and during pregnancy (Exercise); or exercised only during pregnancy (PregEx). Females were mated at 20 weeks, with F2 male kidneys collected (embryonic day 20). Maternal growth restriction alone reduced nephron endowment by 29%, whereas additional lifestyle factors in Restricted dams reduced nephron endowment by ∼43%. Interestingly, Exercise only in High‐fat dams did not alter nephron endowment, which is likely to be attributable to significant kidney remodelling and/or enhanced resource availability. This study demonstrates that growth‐restricted dams that experience multiple maternal lifestyle factors (i.e. High‐fat diet and PregEx) impair the development of male F2 kidneys to a more severe extent than fetuses exposed to maternal growth restriction alone or a single maternal lifestyle factor in dams of normal birth weight (i.e. high‐fat feeding or exercise alone). Importantly, positive lifestyle interventions (Exercise) in a high‐fat environment compounded by adverse metabolic programming (Restriction) can be beneficial to fetal kidney development, which might prevent the transgenerational programming of cardiorenal disease. What is the central question of this study? Uteroplacental insufficiency impairs kidney development, programming male‐onset cardiorenal disease, which can be transmitted transgenerationally. What impact do lifestyle factors in growth‐restricted dams have on second‐generation kidney development? What is the main finding and its importance? Lifestyle factors in growth‐restricted dams compromise fetal nephron endowment to a greater extent than growth restriction alone. Exercise prior to and throughout pregnancy maintains normal nephron endowment in high‐fat dams. Understanding the underlying mechanism(s) might offer therapeutic interventions for infants born small to improve their own and their children's cardiorenal health, breaking the transgenerational cycle.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Animals / Birth weight / Diet, High-Fat / Embryogenesis / exercise / Female / Females / Fetal Development - physiology / Fetal Growth Retardation - physiopathology / Fetus / Fetuses / growth restriction / High fat diet / kidney / Kidney - embryology / Kidneys / Lifestyles / Male / nephron endowment / Nephrons - embryology / Physical Conditioning, Animal - physiology / Placental Insufficiency - physiopathology / Pregnancy / Rats / Rats, Inbred WKY / Resource availability / second generation / Weaning