Comparative Impact of Alternate-Day Fasting and Time-Restricted Feeding on Placental Function and Fetal Development in Maternal Obesity.

Background: Maternal obesity detrimentally affects placental function and fetal development. Both alternate-day fasting (ADF) and time-restricted feeding (TRF) are dietary interventions that can improve metabolic health, yet their comparative effects on placental function and fetal development remain unexplored.

Objectives: This study aims to investigate the effects of ADF and TRF on placental function and fetal development during maternal consumption of a high-fat diet (HFD).

Methods: One hundred 8-week-old female mice were assigned to one of four dietary regimens: (1) normal diet with ad libitum feeding (NA); (2) HFD with ad libitum feeding (HA); (3) HFD with ADF (HI); and (4) HFD with TRF (HT), administered both before and during pregnancy. On gestational day 18.5, serum and placental samples were collected from both mothers and fetuses to examine placental function and fetal development.

Results: During gestation, both ADF and TRF substantially alleviated the metabolic impairments caused by an HFD in obese maternal mice. TRF mice demonstrated enhanced placental nutrient transport and fetal development, associated with reduced endoplasmic reticulum (ER) stress and inflammatory responses. In contrast, ADF markedly intensified placental stress and inflammatory responses, diminished placental nutrient transport efficiency, and consequently induced fetal growth restriction.

Conclusions: Both ADF and TRF during pregnancy significantly mitigated metabolic impairments in obese dams on an HFD. TRF mice demonstrated enhanced placental nutrient transport and fetal development, associated with reduced endoplasmic reticulum (ER) stress and inflammatory responses. In contrast, ADF markedly intensified placental stress and inflammatory responses, diminished placental nutrient transport efficiency, and consequently induced fetal growth restriction.