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In-vitro rat myometrial contractions after oxytocin pretreatment at different trimesters
Abstract Number: OP1-3
Abstract Type: Original Research
Oxytocin receptors in both human and rat myometrial cells are desensitized by exposure to oxytocin, reducing the ability of cells to respond to subsequent administration of oxytocin (1). This desensitization effect reduces oxytocin-induced contractility of the isolated term pregnant rat uterus after pre-treatment with 10-8M concentration of oxytocin for 1h (2). Rat uterine contractility in response to oxytocin has been shown to increase with increased gestational age, both in cell culture and in tissue (3, 4), but the inhibition of contractility after oxytocin pretreatment has heretofore only been explored in the term pregnant rat uterus. The objective of this study was to investigate pregnant rat myometrial contractility in response to oxytocin administration after pretreatment with oxytocin at early gestation (Day 7), mid gestation (Day 14), and term gestation (Day 21-22).
After approval by the Animal Care Committee, this in-vitro study was conducted in pregnant Wistar rats. Four longitudinal myometrial strips were isolated from each animal and after equilibration, were pre-treated with either oxytocin 10-8M or PSS (control) for 1h, then subjected to a dose-response study with oxytocin in a pattern of one log molar increase every 10 min from 10-10M to 10-5M. The amplitude and frequency of contractions were recorded, and the area under the curve (AUC) was calculated and compared between groups.
Myometrial samples were obtained from 27 rats and a total of 67 experiments were performed (oxytocin pre-exposure, n=33; control, n=34). The AUC during the dose-response increased with increasing gestational age (Fig 1). The AUC was significantly higher in the control group vs. oxytocin pre-treated group at term gestation (∆ 70.25%, p = 0.036), but the difference was not significant at early and mid gestation.
These findings agree with our earlier work in term pregnant rat uterus (2). As the desensitization phenomenon does not affect oxytocin-induced myometrial contractility at early and mid gestation, oxytocin can be effectively used as an uterotonic for 1st and 2nd trimester abortions, even after prior oxytocin exposure. Studies in human myometrium are warranted to confirm these findings.
Am J Obstet Gynecol 2003;188:497–502; Reprod Sci 2009;16:501-8; Mol Cell Endocrinol1997;128:77-84; J Physiol 2008;586:6063-76.