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

Nutrients. 2018 Oct 15;10(10):1507. doi: 10.3390/nu10101507.

Abstract

Gestational diabetes mellitus (GDM) is characterized by excessive placental fat and glucose transport, resulting in fetal overgrowth. Earlier we demonstrated that maternal choline supplementation normalizes fetal growth in GDM mice at mid-gestation. In this study, we further assess how choline and its oxidation product betaine influence determinants of placental nutrient transport in GDM mice and human trophoblasts. C57BL/6J mice were fed a high-fat (HF) diet 4 weeks prior to and during pregnancy to induce GDM or fed a control normal fat (NF) diet. The HF mice also received 25 mM choline, 85 mM betaine, or control drinking water. We observed that GDM mice had an expanded placental junctional zone with an increased area of glycogen cells, while the thickness of the placental labyrinth zone was decreased at E17.5 compared to NF control mice (p < 0.05). Choline and betaine supplementation alleviated these morphological changes in GDM placentas. In parallel, both choline and betaine supplementation significantly reduced glucose accretion (p < 0.05) in in vitro assays where the human choriocarcinoma BeWo cells were cultured in high (35.5 mM) or normal (5.5 mM) glucose conditions. Expression of angiogenic genes was minimally altered by choline or betaine supplementation in either model. In conclusion, both choline and betaine modified some but not all determinants of placental transport in response to hyperglycemia in mouse and in vitro human cell line models.

Keywords: betaine; choline; gestational diabetes; nutrient transport; placental morphology; vasculature.

MeSH terms

  • Animal Feed
  • Animals
  • Betaine / administration & dosage*
  • Betaine / metabolism
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Cell Line, Tumor
  • Choline / administration & dosage*
  • Choline / metabolism
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / diet therapy*
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / pathology
  • Diet, High-Fat
  • Dietary Supplements*
  • Disease Models, Animal
  • Energy Metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Maternal-Fetal Exchange
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / genetics
  • Placenta / blood supply*
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Trophoblasts / metabolism
  • Trophoblasts / pathology

Substances

  • Biomarkers
  • Blood Glucose
  • Betaine
  • Choline