C-type natriuretic peptide forms in the ovine fetal and maternal circulations: evidence for independent regulation and reciprocal response to undernutrition.
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.
Prickett
Timothy C R
TC
Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8015, New Zealand. tim.prickett@chmeds.ac.nz
Rumball
Christopher W H
CW
Buckley
Alex J
AJ
Bloomfield
Frank H
FH
Yandle
Timothy G
TG
Harding
Jane E
JE
Espiner
Eric A
EA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting / Q000502:physiology*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005865:Gestational Age; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D020098:Natriuretic Peptide, C-Type / Q000097:blood*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011498:Protein Precursors / Q000097:blood; D012756:Sheep; D014427:Twins; D014508:Urea / Q000097:blood; D014599:Uterus
D001786:Blood Glucose; D007328:Insulin; D011498:Protein Precursors; D020098:Natriuretic Peptide, C-Type; D007334:Insulin-Like Growth Factor I; D014508:Urea