Maternal Choline Supplementation Modulates Placental Nutrient Transport and Metabolism in Late Gestation of Mouse Pregnancy

Abstract

Background: Fetal growth is dependent on placental nutrient supply, which is influenced by placental perfusion and transporter abundance. Previous research indicates that adequate choline nutrition during pregnancy improves placental vascular development, supporting the hypothesis that choline may affect placental nutrient transport. Objective: The present study sought to determine the impact of maternal choline supplementation (MCS) on placental nutrient transporter abundance and nutrient metabolism during late gestation. Methods: Female non-Swiss albino mice were randomly assigned to the 1×, 2×, or 4× choline diet (1.4, 2.8, and 5.6 g choline chloride/kg diet, respectively) 5 d before mating (n = 16 dams/group). The placentas and fetuses were harvested on gestational day (E) 15.5 and E18.5. The placental abundance of macronutrient, choline, and acetylcholine transporters and glycogen metabolic enzymes, and the placental concentration of glycogen were quantified. Choline metabolites and docosahexaenoic acid (DHA) concentrations were measured in the placentas and/or fetal brains. Data were stratified by gestational day and fetal sex and were analyzed by using mixed linear models. Results: At E15.5, MCS downregulated the placental transcript and protein abundance of glucose transporter 1 (GLUT1) (−40% to −73%, P < 0.05) and the placental transcript abundance of glycogen-synthesizing enzymes (−24% to −50%, P ≤ 0.05). At E18.5, MCS upregulated GLUT3 protein abundance (+55%, P = 0.016) and the transcript abundance of glycogen-synthesizing enzymes only in the female placentas (+36% to +60%, P < 0.05), resulting in a doubling (P = 0.01) of the glycogen concentration. A higher placental transcript abundance of the transporters for DHA, choline, and acetylcholine was also detected in response to MCS, consequently altering their concentrations in the placentas or fetal brains (P ≤ 0.05). Conclusions: These data suggest that MCS modulates placental nutrient transporter abundance and nutrient metabolism in late gestation of mouse pregnancy, with subsequent effects on nutrient supply for the developing fetus.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring

“…Based on the intake and choline concentration in water and food, the level of choline supplementation yielded 4.5 times total choline intake in the choline supplemented versus control groups, which has been reported in our previous publication [4]. This supplementation level was demonstrated to improve offspring cognitive development and placental functioning in several studies [4,[24][25][26]. In humans, four times higher choline intake than the Adequate Intake (AI, 450 mg/day for pregnant women) level is achievable by a choline supplement and is within the range of recommended intakes below the upper tolerable intake level of 3500 mg/day [27].…”

“…In humans, four times higher choline intake than the Adequate Intake (AI, 450 mg/day for pregnant women) level is achievable by a choline supplement and is within the range of recommended intakes below the upper tolerable intake level of 3500 mg/day [27]. supplementation level was demonstrated to improve offspring cognitive development and placental functioning in several studies [4,[24][25][26]. In humans, four times higher choline intake than the Adequate Intake (AI, 450 mg/day for pregnant women) level is achievable by a choline supplement and is within the range of recommended intakes below the upper tolerable intake level of 3500 mg/day [27].…”

Curcumin Protects Human Trophoblast HTR8/SVneo Cells from H2O2-Induced Oxidative Stress by Activating Nrf2 Signaling Pathway

“…The enhanced activation of Nrf2 signaling could also explain for the increased activity of CAT and decreased accumulation of ROS. In addition, up-regulation of nutrient transporters (SLC2A3) can improve the transfer of nutrients (including amino acids, fatty acids, and glucose) from mother to fetus, which plays an important role in placental development and fetal growth [54,55]. In our previous in vivo experiment, we have proven that curcumin has beneficial effects on nutrient transport and placental development, which could be applied for alleviating IUGR of mice.…”

Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts

“…There was no betaine in the diets. The dosages of choline/betaine supplementation were chosen based on prior studies, demonstrating that choline supplementation at the selected dosage improves cognitive development and placental function, while betaine supplementation at the current dosage reduces the hepatic injury due to HF-feeding [ 29 , 31 , 32 ]. Female mice were fed one of the diets from 4 weeks before timed-mating to embryonic day E12.5 or E17.5 of gestation.…”

“…We further provide evidence to support the potential mechanism in which choline and betaine modify fetal growth in GDM mice via alterations in placental functioning, such as downregulating the placental growth promoter insulin-like growth factor 2 ( Igf2 ), suppressing the mechanistic target of rapamycin (mTOR) signaling or reducing macronutrient transporter expression [ 23 , 24 , 25 ]. Literature also suggests that maternal choline supplementation alters DNA methylation and angiogenesis in human and rodent placentas and/or trophoblasts [ 26 , 27 , 28 , 29 , 30 ].…”