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孕妇肥胖与胎盘牛磺酸转运体活性降低有关。

Maternal obesity is associated with a reduction in placental taurine transporter activity.

作者信息

Ditchfield A M, Desforges M, Mills T A, Glazier J D, Wareing M, Mynett K, Sibley C P, Greenwood S L

机构信息

1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

出版信息

Int J Obes (Lond). 2015 Apr;39(4):557-64. doi: 10.1038/ijo.2014.212. Epub 2014 Dec 30.

Abstract

BACKGROUND/OBJECTIVES: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m(-)(2)) than in women of ideal weight (BMI 18.5-24.9 kg m(-)(2)) and explored potential regulatory factors.

SUBJECTS/METHODS: Placentas were collected from term (37-42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19-49 kg m(-)(2). TauT activity was measured as the Na(+)-dependent uptake of (3)H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity.

RESULTS

Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.

CONCLUSIONS

Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome.

摘要

背景/目的:孕妇肥胖会增加不良妊娠结局的风险,包括死产、先兆子痫、胎儿生长受限和胎儿过度生长。这些妊娠并发症与合体滋养层细胞功能失调有关,合体滋养层细胞是人类胎盘的转运上皮细胞。牛磺酸是一种具有抗氧化和细胞保护特性的β-氨基酸,在合体滋养层细胞的发育和功能中发挥作用,是胎儿生长和器官发育所必需的。牛磺酸在孕期为条件必需氨基酸,胎儿组织依赖于从母体血液中摄取牛磺酸。我们检验了以下假设:肥胖女性(体重指数(BMI)⩾30 kg·m⁻²)胎盘合体滋养层细胞通过牛磺酸转运蛋白(TauT)摄取牛磺酸的能力低于理想体重女性(BMI 18.5 - 24.9 kg·m⁻²),并探讨了潜在的调节因素。

对象/方法:收集孕周为37 - 42周、无并发症的单胎妊娠孕妇的胎盘,这些孕妇的BMI为19 - 49 kg·m⁻²。通过测量³H - 牛磺酸向胎盘绒毛片段的Na⁺依赖性摄取来测定TauT活性。采用蛋白质免疫印迹法研究富含膜的胎盘样本中TauT的表达。使用胎盘绒毛外植体进行的体外研究,检验了瘦素或IL - 6(这两种在孕妇肥胖时升高的脂肪因子/细胞因子)是否调节TauT活性。

结果

肥胖女性(BMI⩾30)的胎盘TauT活性显著低于理想体重女性(P<0.03),且与孕妇BMI呈负相关(19 - 49 kg·m⁻²;P<0.05;n = 61)。理想体重胎盘与肥胖III级(BMI⩾40)受试者的胎盘之间,TauT表达无差异。胎盘绒毛外植体长期(48小时)暴露于瘦素或IL - 6不影响TauT活性。

结论

足月时胎盘TauT活性与孕妇BMI呈负相关。我们认为,孕妇肥胖时胎盘TauT活性降低可能会降低合体滋养层细胞牛磺酸浓度,损害胎盘发育和功能,并降低牛磺酸向胎儿外流的驱动力,从而增加不良妊娠结局的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11b0/4389721/2f80d84452a8/ijo2014212f1.jpg

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