C-Type Natriuretic Peptide Forms in Pregnancy: Maternal Plasma Profiles during Ovine Gestation Correlate with Placental and Fetal Maturation

Circulating concentrations of C-type natriuretic peptide (CNP) and a related amino terminal fragment (NTproCNP) were measured at weekly intervals from preconception to 3 wk postpartum in ewes with twins (n = 8) and nonpregnant ewes (n = 8). In contrast to low and stable values in nonpregnant ewes (CNP, 0.75 +/- 0.08; NTproCNP, 22 +/- 2 pmol/liter), CNP forms increased abruptly at 40-50 d of gestation and rose to peak values (CNP, 31 +/- 5, NTproCNP, 270 +/- 16 pmol/liter) at about d 120. Approximately 7 d prepartum, the concentration of both CNP forms fell precipitously to preconception values immediately postpartum. In separate studies, circulating maternal CNP forms were positively related to fetal number at d 120. Consistent with a major contribution from the placenta to circulating levels, the concentrations of CNP forms were elevated in the placentome (cotyledon: CNP, 18 +/- 4, NTproCNP, 52 +/- 10 pmol/g; caruncle: CNP, 13 +/- 3, NTproCNP, 31 +/- 6 pmol/g) and much higher than those of intercaruncular uterine tissue (CNP, 0.19 +/- 0.05, NT-proCNP, 0.98 +/- 0.2 pmol/g) in late-gestation ewes (P < 0.001, n = 4). These distinctive patterns of maternal plasma CNP forms, positive relation with fetal number, and greatly elevated protein concentrations in the placentome demonstrate the hormone's strong relation to placental and fetal maturation. The findings provide a firm basis for future studies of the functional role of CNP in fetal-maternal welfare. (Endocrinology 150: 4777-4783, 2009)