Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
Pediatr Res. 2013 Apr;73(4 Pt 1):388-94. doi: 10.1038/pr.2013.14. Epub 2013 Jan 21.
The mechanisms whereby gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth and development of metabolic diseases later in life are likely to involve changes in nutrient supply to the fetus. Hence, in this work, we hypothesize that GDM may affect folic acid (FA) supply to the placenta and fetus.
We compared (3)H-FA uptake by human cytotrophoblasts isolated from normal pregnancies (normal trophoblasts; NTB cells) and GDM pregnancies (diabetic trophoblasts; DTB cells) and investigated the effect of GDM hallmarks on (3)H-FA uptake by BeWo cells.
(3)H-FA uptake by NTB and DTB cells was time dependent and acidic pH stimulated. When compared with NTB, (3)H-FA uptake by DTB cells was more sensitive to acidic pH changes and to 5-methyltetrahydrofolate and pemetrexed (PTX) inhibition, indicating a proportionally greater involvement of the proton-coupled folate transporter (PCFT). A 4-h exposure of BeWo cells to lipopolysaccharide (LPS, 1-10 μg/ml) or to high levels of tumor necrosis factor-α (TNF-α, 300 ng/l) significantly reduced (3)H-FA uptake. Moreover, hyperleptinemic conditions (100 ng/ml leptin) decreased (3)H-FA uptake by BeWo cells in a time-dependent manner when compared with normoleptinemic conditions (1 ng/ml leptin).
GDM modulates (3)H-FA uptake by the syncytiotrophoblast, and leptin as well as TNF-α downregulate it.
妊娠糖尿病（GDM）增加胎儿过度生长和日后发生代谢性疾病风险的机制可能涉及到胎儿营养供应的变化。因此，在这项工作中，我们假设 GDM 可能会影响胎盘和胎儿的叶酸（FA）供应。
我们比较了来自正常妊娠（正常滋养细胞；NTB 细胞）和 GDM 妊娠（糖尿病滋养细胞；DTB 细胞）的人绒毛膜滋养层细胞对（3）H-FA 的摄取，并研究了 GDM 标志物对 BeWo 细胞摄取（3）H-FA 的影响。
NTB 和 DTB 细胞对（3）H-FA 的摄取随时间呈依赖性增加，酸性 pH 刺激增加。与 NTB 相比，DTB 细胞对酸性 pH 变化和 5-甲基四氢叶酸和培美曲塞（PTX）的抑制作用更敏感，表明质子偶联叶酸转运体（PCFT）的参与比例更大。BeWo 细胞暴露于脂多糖（LPS，1-10 μg/ml）或高浓度肿瘤坏死因子-α（TNF-α，300 ng/l）4 小时显著降低了（3）H-FA 的摄取。此外，与正常瘦素水平（1 ng/ml 瘦素）相比，高瘦素血症条件（100 ng/ml 瘦素）以时间依赖性方式降低了 BeWo 细胞对（3）H-FA 的摄取。
GDM 调节合体滋养层细胞对（3）H-FA 的摄取，瘦素和 TNF-α 下调其摄取。
