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, where maternal nutrition is crucial to normal growth and development. We therefore studied maternal and fetal CNP and the aminoterminal (bio-inactive) fragment NTproCNP in 39 chronically catheterized pregnant sheep before and after a 3 day 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. Utero-placental production of CNP was suggested by a high veno-arterial concentration gradient across the gravid uterus, and a correlation between maternal NTproCNP levels and placental weight (r²=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 utero-placental unit to substrate deficiency. CNP may have a role in maintaining fetal welfare, and provide a possible marker of utero-placental nutrient supply.