Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats

Abstract

The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways.

SAM/SAH Mediates Parental Folate Deficiency-Induced Neural Cell Apoptosis in Neonatal Rat Offspring: The Expression of Bcl-2, Bax, and Caspase-3

“…Maternal folate deficiency is understood to impact the neurodevelopment and brain health of the offspring, potentially leading to neurodevelopmental disorders, including neural tube defects [43]. However, the mechanisms by which maternal folate levels affect offspring's neurodevelopment, including DNA methylation [44], oxidative stress [45], inflammation [46], etc., are complex and inconclusive. Nevertheless, the relationship between paternal folate intake and fetal brain development has very rarely been reported.…”

Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota

“…Western blotting was conducted in accordance with previously established protocols [23]. The protein content was quantified using the BCA Protein Assay Kit (Beyotime, Zhenjiang, China).…”

Exploring the Role of Mediterranean and Westernized Diets and Their Main Nutrients in the Modulation of Oxidative Stress in the Placenta: A Narrative Review

“…Folic acid supplementation was found to attenuate the consequences of an unhealthy diet, with an increase in the expression of Nrf2 and SIRT1 and downregulation of NF-κB. Other investigated effects included the alleviation of angiogenesis factors, blood sinusoid area, and damage to vascular density caused by diet-induced placental vascular dysplasia [164].…”