Oxytocin hypersensitivity in pregnant P-LAP deficient mice

Mar 3, 2009Life sciences

Increased sensitivity to oxytocin in pregnant mice lacking P-LAP enzyme

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Abstract

A significant shortening of pregnancy term was observed in P-LAP KO mice.

Continuous infusion of oxytocin (1 U/day) led to premature delivery in P-LAP KO mice, indicating hypersensitivity to oxytocin.
Administration of arginine vasopressin (1 U/day) resulted in a significant decrease in urine volume in P-LAP KO mice.
Recombinant placental leucine aminopeptidase in wild type mice delayed the onset of labor by approximately 1.5 days compared to controls.
The regulation of labor onset appears to be influenced by oxytocin and its degradation by placental leucine aminopeptidase.

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AIMS: Oxytocin (OT) is the strongest uterotonic substance and has been used widely to induce labor. The physiological importance of OT in modulating the initiation and progression of labor remains unclear. In this study, we showed the roles of OT with onset of labor and also the arginine vasopressin (AVP) effect on urine volume in vivo using both wild type (WT) and placental leucine aminopeptidase (P-LAP)-deficient (KO) mice.

MAIN METHODS: OT (1, 2, 2.5 U/day) or recombinant P-LAP (0.01 U/day) was continuously infused from gestation day 15.5 in WT and P-LAP KO mice. Duration until onset of labor was observed. Before and after administration of AVP (1 U/day) in WT and P-LAP KO mice, urine volume was measured.

KEY FINDINGS: A significant shortening of pregnancy term was observed in P-LAP KO mice. Continuous infusion of OT (1 U/day) revealed that P-LAP KO mice resulted in premature delivery (OT hypersensitivity). We could observe a significant decrease of urine volume in P-LAP KO mice by administration of AVP. Administration of recombinant P-LAP in WT mice resulted in the delay of the onset of labor about 1.5 days compared with control mice.

SIGNIFICANCE: Our present study shows that the regulation of the onset of labor mainly depends on OT and its degradation by P-LAP and also the possible role of P-LAP in the regulation of urine output. P-LAP might be involved in the increased OT sensitivity just prior to onset of labor and also in the onset of labor by degradation of OT.

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Oxytocin hypersensitivity in pregnant P-LAP deficient mice

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