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

Abstract

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, NTproCNP, 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.

Effect of Cortisol on C-Type Natriuretic Peptide in Ovine Pregnancy: Differential Responses in Fetal and Placental Tissues

“…In contrast, the ovine placenta does not seem to contribute to circulating fetal CNP concentrations, which are much lower than maternal concentrations (12). Nonetheless, as in the human fetus (13), fetal CNP synthesis is likely to be high, as shown by the very high concentrations of NTproCNP in fetal plasma.…”

“…Recent studies of ovine pregnancy show that both CNP and the bio inactive aminoterminal fragment of pro CNP 1-103 (NTproCNP) (11) are secreted by the placenta and circulate at high concentrations in maternal plasma from the end of the first trimester (12). In contrast, the ovine placenta does not seem to contribute to circulating fetal CNP concentrations, which are much lower than maternal concentrations (12).…”

“…Peptide standards were made from synthetic human proCNP (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), taking into account the purity data supplied (Chiron Technologies, Victoria, Australia).Within-and between-assay coefficients of variation were 4.9 and 6.4%, respectively, at 22 pmol/L.…”

Sustained increases in plasma C-type natriuretic peptides fail to increase concentrations in cerebrospinal fluid: Evidence from pregnant sheep

“…Rabbit antiserum J39, raised against human proCNP (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), was used as the primary antibody. Since the sequence of ovine and human proCNP (1-15) differs at amino acid residue 14, concentrations obtained using the new ovine standard also differ from those previously reported [16]. The following formula describes the numeric relationship for sheep plasma concentration read from human vs sheep NTproCNP standard curves: [log sheep NTproCNP] = 1.4 [log human NTproCNP] − 0.30.…”

“…Hypothesizing that CSF concentrations of CNP will not be changed by sustained elevations in the systemic circulation, we have now measured CNP forms in time-matched samples of CSF and venous plasma obtained from pregnant sheep -a physiologically unique setting in which the circulating concentrations of CNP forms in blood are markedly increased for prolonged periods [16]. gestation and peptide concentrations were compared with values in 15 non pregnant control ewes similarly sampled over the same time period.…”