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胎盘瘦素:子宫内及新生儿发育中的一种重要新生长因子?

Placental leptin: an important new growth factor in intrauterine and neonatal development?

作者信息

Hassink S G, de Lancey E, Sheslow D V, Smith-Kirwin S M, O'Connor D M, Considine R V, Opentanova I, Dostal K, Spear M L, Leef K, Ash M, Spitzer A R, Funanage V L

机构信息

Department of Pediatrics, Alfred I. duPont Institute, Wilmington, DE 19803, USA.

出版信息

Pediatrics. 1997 Jul;100(1):E1. doi: 10.1542/peds.100.1.e1.

DOI:10.1542/peds.100.1.e1
PMID:9200375
Abstract

BACKGROUND

Leptin, the protein product of the ob gene, is produced by the adipocyte and seems to function as a link between adiposity, satiety, and activity. Leptin has also been found to be necessary for pubertal development, conception, and pregnancy in mice, and is increased in prepubertal children, independent of adiposity, suggesting a role in childhood growth and development. This study investigated 100 mother/newborn pairs to determine the role of leptin in neonatal development. Placental tissue was assayed for leptin mRNA to evaluate it as a source of leptin production in utero.

METHODS

One hundred mother/newborn pairs were enrolled in this study. Radioimmunoassay was performed for leptin on maternal venous and newborn cord blood. Leptin concentrations were measured in 43 children in Tanner stages 1 and 2 as a control group. Placental tissue was obtained from five mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Human placental cell lines JAR and JEG-3 were also assayed for leptin mRNA expression.

RESULTS

Leptin was present in all newborns studied at a mean concentration of 8.8 ng/mL (+/-9.6 standard deviations). Leptin concentrations in cord blood correlated with newborn weight (r = .51), body mass index (BMI) (r = .48), and arm fat (r = .42). There was no correlation between leptin and insulin. When statistically covarying for adiposity for newborns and Tanner stages 1 and 2 children, newborns had greater concentrations of leptin (mean, 10.57 ng/mL) than children (mean, 3.04 ng/mL). Leptin was present in all mothers at a mean value of 28.8 ng/mL (+/-22.2 standard deviations). Leptin concentration correlated with prepregnancy BMI (r = .56), BMI at time of delivery (r = .74), and arm fat (r = .73). Maternal leptin correlated with serum insulin (r = .49). There was no correlation between maternal and newborn leptin concentrations. Thirteen percent of newborns had higher leptin concentrations than their mothers. Placental tissue from five separate placentas expressed leptin mRNA at comparable or greater levels than adipose tissue. Two human trophoblastic placental cell lines, JAR and JEG-3, also expressed leptin mRNA.

CONCLUSIONS

The correlation between leptin and adiposity found in children and adults was also found in newborns. Serum leptin concentrations in newborns were increased more than three-fold compared with children in Tanner stages 1 and 2 when controlling for adiposity, suggesting that leptin concentrations in the newborn are not explained by adiposity alone. Maternal leptin concentrations correlated with measures of adiposity at delivery but did not correlate with newborn adiposity or leptin. Leptin mRNA was expressed both in placental tissue and in two human placental cell lines. These data suggest that leptin has a role in intrauterine and neonatal development and that the placenta provides a source of leptin for the growing fetus.

摘要

背景

瘦素是肥胖基因的蛋白质产物,由脂肪细胞产生,似乎起着肥胖、饱腹感和活动之间的联系作用。在小鼠中还发现瘦素对青春期发育、受孕和妊娠是必需的,并且在青春期前儿童中增加,与肥胖无关,提示其在儿童生长发育中起作用。本研究调查了100对母婴,以确定瘦素在新生儿发育中的作用。检测胎盘组织中的瘦素mRNA,以评估其作为子宫内瘦素产生来源的情况。

方法

100对母婴纳入本研究。对母体静脉血和新生儿脐带血进行瘦素放射免疫测定。对43名处于坦纳1期和2期的儿童进行瘦素浓度测量作为对照组。从5名母亲获取胎盘组织,通过逆转录/聚合酶链反应(RT/PCR)检测瘦素mRNA。还检测了人胎盘细胞系JAR和JEG-3的瘦素mRNA表达。

结果

在所研究的所有新生儿中均存在瘦素,平均浓度为8.8 ng/mL(±9.6标准差)。脐带血中的瘦素浓度与新生儿体重(r = 0.51)、体重指数(BMI)(r = 0.48)和手臂脂肪(r = 0.42)相关。瘦素与胰岛素之间无相关性。在对新生儿以及坦纳1期和2期儿童的肥胖进行统计学协变量调整后,新生儿的瘦素浓度(平均10.57 ng/mL)高于儿童(平均3.04 ng/mL)。所有母亲均存在瘦素,平均值为28.8 ng/mL(±22.2标准差)。瘦素浓度与孕前BMI(r = 0.56)、分娩时BMI(r = 0.74)和手臂脂肪(r = 0.73)相关。母体瘦素与血清胰岛素相关(r = 0.49)。母体和新生儿瘦素浓度之间无相关性。13%的新生儿瘦素浓度高于其母亲。来自5个不同胎盘的胎盘组织表达瘦素mRNA的水平与脂肪组织相当或更高。两个人类滋养层胎盘细胞系JAR和JEG-3也表达瘦素mRNA。

结论

在儿童和成人中发现的瘦素与肥胖之间的相关性在新生儿中也存在。在控制肥胖的情况下,新生儿血清瘦素浓度比坦纳1期和2期的儿童增加了三倍多,表明新生儿的瘦素浓度不能仅用肥胖来解释。母体瘦素浓度与分娩时的肥胖指标相关,但与新生儿肥胖或瘦素无关。瘦素mRNA在胎盘组织和两个人类胎盘细胞系中均有表达。这些数据表明瘦素在子宫内和新生儿发育中起作用,并且胎盘为发育中的胎儿提供了瘦素来源。

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