Distinct and stage-specific effects of pre-pregnancy and gestational high-fat diet on maternal metabolism, placental adaptation and gut microbiota in rats.

BACKGROUND

Maternal high-fat diet (HFD) contributes to developmental programming through placental adaptations; however, the effects of exposure timing before and during pregnancy remain unclear.

OBJECTIVE

To investigate the distinct effects of pre-pregnancy and gestational HFD on maternal metabolism, pregnancy outcomes, placental oxidative stress, placental gene-expression adaptations, and gut microbiota in rats.

METHODS

Female Sprague-Dawley rats were fed a control diet (V) or HFD (H) before and/or during pregnancy, generating four groups (V/V, V/H, H/V, H/H). Maternal metabolic parameters, placental gene expression, oxidative stress, and gut microbiota composition were analyzed at gestational day 21.

RESULTS

Pre-pregnancy high-fat diet increased maternal body and liver weights and elevated placental oxidative stress, whereas gestational high-fat diet increased adiposity and impaired glucose tolerance and insulin sensitivity without affecting pregnancy outcomes. Placental nutrient transporters, including glucose transporter 1 (Glut1) and solute carrier family 38 (Slc38) members, were mainly regulated by pre-pregnancy diet. Insulin-like growth factor 2 (Igf2) was influenced by gestational diet and its interaction with pre-pregnancy diet, while insulin-like growth factor 2 receptor (Igf2R) and insulin 2 (Ins2) expression were primarily influenced by pre-pregnancy diet. Forkhead box O1 (FoxO1) and Forkhead box O3 (FoxO3) exhibited differential responses to maternal dietary exposure. Gestational HFD also altered gut microbiota composition without affecting microbial diversity.

CONCLUSION

Pre-pregnancy and gestational HFD exert distinct but complementary effects on maternal metabolism and placental adaptations. These findings highlight the stage-specific impact of maternal nutritional status on developmental programming and placental function.