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

Maternal Choline and Betaine Supplementation Modifies the Placental Response to Hyperglycemia in Mice and Human Trophoblasts.
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DOI:
10.3390/nu10101507
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发表时间:
2018-10-15
期刊:
影响因子:
5.9
通讯作者:
Jiang X
Jiang X
中科院分区:
医学2区
文献类型:
--
作者:
Nanobashvili K;Jack-Roberts C;Bretter R;Jones N;Axen K;Saxena A;Blain K;Jiang X

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妊娠期糖尿病(GDM)的特点是胎盘脂肪和葡萄糖转运过多,导致胎儿过度生长。早些时候,我们证明母体补充胆碱可以使妊娠中期 GDM 小鼠的胎儿生长正常化。在这项研究中,我们进一步评估了胆碱及其氧化产物甜菜碱如何影响 GDM 小鼠和人类滋养层胎盘营养转运的决定因素。 C57BL/6J 小鼠在怀孕前 4 周和怀孕期间喂食高脂肪 (HF) 饮食以诱导 GDM,或喂食对照正常脂肪 (NF) 饮食。 HF 小鼠还接受 25 mM 胆碱、85 mM 甜菜碱或对照饮用水。我们观察到,与 NF 对照小鼠相比,GDM 小鼠的胎盘交界区扩大,糖原细胞面积增加,而胎盘迷路区的厚度在 E17.5 时减少(p < 0.05)。胆碱和甜菜碱的补充减轻了 GDM 胎盘的这些形态变化。与此同时,在体外试验中,在高(35.5 mM)或正常(5.5 mM)葡萄糖条件下培养人绒毛膜癌 BeWo 细胞,补充胆碱和甜菜碱均显着降低葡萄糖积累(p < 0.05)。在这两种模型中,补充胆碱或甜菜碱对血管生成基因的表达影响很小。总之,在小鼠和体外人类细胞系模型中,胆碱和甜菜碱都改变了响应高血糖的胎盘转运的一些但不是全部决定因素。
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.
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