de Vrijer Barbra, Regnault Timothy R H, Wilkening Randall B, Meschia Giacomo, Battaglia Frederick C
University of Colorado Health Sciences Center, Dept. of Pediatrics, Division of Perinatal Medicine, PO Box 6508-F441, Aurora, CO 80045, USA.
Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1114-24. doi: 10.1152/ajpendo.00259.2004. Epub 2004 Aug 17.
Reductions in fetal plasma concentrations of certain amino acids and reduced amino acid transport in vesicle studies suggest impaired placental amino acid transport in human fetal growth restriction (FGR). In the present study, we tested the hypothesis of an impairment in amino acid transport in the ovine model of hyperthermia-induced FGR by determining transplacental and placental retention and total placental clearance of a branched-chain amino acid (BCAA) analog, the nonmetabolizable neutral amino acid aminocyclopentane-1-carboxylic acid (ACP), in singleton control (C) and FGR pregnancies at 135 days gestation age (dGA; term 147 dGA). At study, based on the severity of the placental dysfunction, FGR fetuses were allocated to severe (sFGR, n = 6) and moderate FGR (mFGR, n = 4) groups. Fetal (C, 3,801.91 +/- 156.83; mFGR, 2,911.33 +/- 181.35; sFGR, 1,795.99 +/- 238.85 g; P < 0.05) and placental weights (C, 414.38 +/- 38.35; mFGR, 306.23 +/- 32.41; sFGR, 165.64 +/- 28.25 g; P < 0.05) were reduced. Transplacental and total placental clearances of ACP per 100 g placenta were significantly reduced in the sFGR but not in the mFGR group, whereas placental retention clearances were unaltered. These data indicate that both entry of ACP into the placenta and movement from the placenta into fetal circulation are impaired in severe ovine FGR and support the hypothesis of impaired placental BCAA transport in severe human FGR.
胎儿血浆中某些氨基酸浓度降低以及囊泡研究中氨基酸转运减少，提示人类胎儿生长受限（FGR）时胎盘氨基酸转运受损。在本研究中，我们通过测定单胎对照（C）和妊娠135天胎龄（dGA；足月为147 dGA）的FGR妊娠中一种支链氨基酸（BCAA）类似物、不可代谢的中性氨基酸氨基环戊烷-1-羧酸（ACP）的跨胎盘转运、胎盘潴留及胎盘总清除率，来检验热应激诱导的FGR绵羊模型中氨基酸转运受损的假说。在研究时，根据胎盘功能障碍的严重程度，将FGR胎儿分为重度（sFGR，n = 6）和中度FGR（mFGR，n = 4）组。胎儿体重（C组，3801.91±156.83；mFGR组，2911.33±181.35；sFGR组，1795.99±238.85 g；P < 0.05）和胎盘重量（C组，414.38±38.35；mFGR组，306.23±32.41；sFGR组，165.64±28.25 g；P < 0.05）均降低。每100 g胎盘的ACP跨胎盘转运及胎盘总清除率在sFGR组显著降低，但在mFGR组未降低，而胎盘潴留清除率未改变。这些数据表明，在重度绵羊FGR中，ACP进入胎盘以及从胎盘进入胎儿循环均受损，支持重度人类FGR中胎盘BCAA转运受损的假说。
