Human placental transport of oxytocin

Abstract

Oxytocin (OX) has been suggested as a signal for parturition. Although OX is produced by both mother and fetus, concentrations are higher in umbilical than maternal blood. In addition, umbilical artery OX concentrations (15–40 pg/ml) are higher than umbilical vein (4–12 pg/ml) and maternal (1–10 pg/ml) concentrations. The umbilical A‐V difference suggests that placental uptake and transport may be one path from fetal (F) to maternal (M) circulation. However, this difference may also reflect placental oxytocinase activity, which is known to metabolize biologically active peptides such as OX. We have investigated placental transport of OX from F to M and M to F circulation using in vitro dually perfused isolated cotyledons from term human placenta. Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. A single peripheral cotyledon and corresponding lobule was cannulated and perfused. After stabilization and demonstration of adequate M to F perfusion perfusion overlap, we studied the transport of OX (3H) with 14C‐inulin (14C‐IN) as permeability reference in both M to F (n=8) and F to M (n= 6) directions during 2 h of perfusion. In addition to the higher tissue uptake observed in M to F than F to M transport direction as measured by the drop in the concentration of both 3H‐OX and 14C‐IN in the circuits in which both compounds were added, the same trend was found for the transfer rates of both compounds. These transfer rates which reflect the permeability of placental tissue to OX and IN were 15.17 ± 2.79 (mean ± SD) and 6.28 ± 0.93 μl/min/g (M to F) and 11.79 ± 1.77 and 4.91 ± 0.81 μl/min/g (F to M). Although the permeability of both compounds is higher in the M to F than in the F to M transport direction, comparing these permeability values with respect to their molecular weight (MW) showed a significant correlation when known permeability values of polar compounds between MW 60 and 68,000 daltons were included. This correlation indicates that OX crosses the placenta in both directions by simple diffusion. High‐performance liquid chromatography analysis showed that here is little evidence of placental metabolism and degradation of OX over the period of these experiments. Oxytocin is the main therapeutic drug that is frequently used in obstetrics for the induction of labor and parturition. Under such circumstances and with respect to the placental permeability results, oxytocin could reach the fetal circulation. © 1996 Wiley‐Liss, Inc.

Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain

“…However it is unclear if the peptide is transported transplacentally. In both pregnant rats and humans, relatively high levels of oxytocin are found in the amniotic fluid and umbilical blood near term [30,31] but it is unclear if this is derived from transplacental transport. Oosterbaan et al [32] reported that oxytocin infusion to Wistar rat dams in late pregnancy did not alter amniotic fluid levels of the peptide.…”

“…Oosterbaan et al [32] reported that oxytocin infusion to Wistar rat dams in late pregnancy did not alter amniotic fluid levels of the peptide. However, using perfused term human placentae, Malek et al [30] provided evidence for transplacental diffusion of oxytocin from maternal to fetal circulation. In contrast, Patient et al [33] found no evidence of transplacental oxytocin transfer by measuring the peptide in umbilical artery and vein during oxytocin infusion to term pregnant women.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…ELS-associated decreases in peripheral and central OT may have an effect on mediators of MPF stress biology (e.g., HPA axis and immune system) and could therefore affect fetal development in utero . Also, OT is able to pass the placenta (Malek et al, 1996) and may thus serve as a signal to the fetus of (early) maternal experiences and the quality of the postnatal environment. There is also evidence suggesting that parenting behavior and risk for PPD is already prepared for during pregnancy through alterations in OT pathways (Feldman et al, 2007; Skrundz et al, 2011), and it is plausible to assume that gestational oxytocinergic adaptations mediate the link between ELS and postnatal maternal behavior.…”

“…Importantly, OT itself was shown to pass the placental barrier by means of passive diffusion in vitro (Malek et al, 1996) to potentially participate in fetal brain development and could therefore constitute a possible mother-to-fetus signaling pathway conveying information to the fetus about (early) maternal experiences and the quality of the postnatal environment. However, others could not confirm OT passage across the placenta in vivo (Patient et al, 1999).…”

Effects of oxytocin used during delivery on development: A retrospective cohort study

“…Some studies also suggest that oxytocin receptors are expressed by neurons in different parts of the brain (Carter, 2007;Zingg & Laporte, 2003) and postulate that excess circulating oxytocin may cross the placental barrier (Malek, Blann, & Mattison, 1996), reach the brain through the bloodstream, and desensitize oxytocin receptors (Gressens, Mesples, Sahir, Marret, & Sola, 2001) causing negative effects on the newborns (Anagnostakis, Messaritakis, Damianos, & Mandyla, 1992;Khazipov, Tyzio & Ben-Ari, 2008;Olza Fernandez et al, 2012;Saunders, Habgood, & Dziegielewska, 1999), or their mothers (García-Fortea et al, 2014;Jonas et al, 2009;Odent, 2013;Zink & Meyer-Lindenberg, 2012).…”