Prickett Timothy C R, Rumball Christopher W H, Buckley Alex J, Bloomfield Frank H, Yandle Timothy G, Harding Jane E, Espiner Eric A
Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8015, New Zealand.
Endocrinology. 2007 Aug;148(8):4015-22. doi: 10.1210/en.2007-0281. Epub 2007 May 17.
C-type natriuretic peptide (CNP) has a crucial role in postnatal endochondral bone growth and is rapidly responsive to changes in nutrition. Although CNP is expressed in the placenta, little is known about the regulation and role of CNP in fetal-maternal health. We hypothesized that CNP may be similarly responsive to undernutrition in the growing fetus, in which maternal nutrition is crucial to normal growth and development. We therefore studied maternal and fetal CNP and the aminoterminal (bioinactive) fragment of proCNP (NTproCNP) in 39 chronically catheterized pregnant sheep before and after a 3-d maternal fast from 121 d gestation. Maternal CNP and NTproCNP levels were higher than in the fetus (CNP 12-fold, NTproCNP 1.5-fold, both P < 0.001). The ratio of NTproCNP to CNP was higher in the fetus than the mother (53 +/- 3 vs. 8.7 +/- 0.6, P < 0.001), suggesting enhanced synthesis and/or degradation of CNP in the fetus. As in postnatal lambs, fetal plasma CNP forms fell promptly during maternal fasting. In contrast, maternal levels exhibited reciprocal and contemporaneous increase, which was reversed by refeeding. Uteroplacental production of CNP was suggested by a high venoarterial concentration gradient across the gravid uterus, and a correlation between maternal NTproCNP levels and placental weight (r(2) = 0.26, P = 0.01). These studies provide the first evidence that CNP is regulated independently in the fetus. Reciprocal increases in maternal CNP forms may reflect the response of the uteroplacental unit to substrate deficiency. CNP may have a role in maintaining fetal welfare and provides a possible marker of uteroplacental nutrient supply.
C型利钠肽（CNP）在出生后软骨内骨生长中起关键作用，并且对营养变化反应迅速。尽管CNP在胎盘中表达，但关于CNP在母婴健康中的调节作用和功能知之甚少。我们推测，在生长中的胎儿中，CNP可能同样对营养不足有反应，而母体营养对胎儿的正常生长发育至关重要。因此，我们研究了39只长期插管的怀孕绵羊在妊娠121天开始禁食3天后，母体和胎儿的CNP以及前体CNP的氨基末端（无生物活性）片段（NTproCNP）。母体CNP和NTproCNP水平高于胎儿（CNP高12倍，NTproCNP高1.5倍，均P<0.001）。胎儿中NTproCNP与CNP的比值高于母体（53±3对8.7±0.6，P<0.001），提示胎儿中CNP的合成和/或降解增强。与出生后的羔羊一样，母体禁食期间胎儿血浆CNP水平迅速下降。相反，母体水平呈现相反且同步的升高，重新喂食后恢复正常。妊娠子宫动静脉之间的高浓度梯度以及母体NTproCNP水平与胎盘重量之间的相关性（r² = 0.26，P = 0.01）提示子宫胎盘可产生CNP。这些研究首次证明CNP在胎儿中是独立调节的。母体CNP水平的反向升高可能反映了子宫胎盘单位对底物缺乏的反应。CNP可能在维持胎儿健康方面发挥作用，并可能是子宫胎盘营养供应的一个标志物。
