Myometrial Response to Oxytocin Is Affected by Parity

Objective The complex array of hormonal interactions that develop during pregnancy exert a profound impact in the reproductive system and in various other aspects of a woman's physiology. Some systems are permanently changed via epigenetic DNA modification, as it has been shown recently in the mammary gland (dos Santos, 2015). The aim of the present study was to investigate the hypothesis that pregnancy can affect some aspects of the uterine function, as well. Thus, we compared the response of non‐pregnant myometrium harvested from virgin and parous female rats to increasing concentrations of oxytocin, PGE2, and PGF2, which are endogenous stimulators of contractility in the uterus. Methods Virgin and parous female non‐pregnant CD Sprague Dawley rats (Charles River Laboratories) were euthanized at 18 weeks of age (to eliminate the confounding effect of age on contractility measurements) during proestrus (to eliminated variability due to hormonal fluctuations). The uterine horns were removed and one was flash frozen for later use (ELISA), while the other was dissected into six 3×10 mm strips. These were then suspended in a tissue bath containing Krebs solution (in mM, NaCl 117, KCl 4.7, NaHCO 3 25, MgCl 2 1.2, KH 2 PO 4 1.2, CaCl 2 2.5, glucose 11, pH= 7.4) at 37°C and bubbled with 95% O2 and 5% CO2. Separate dose responses curves to oxytocin, PGE2, and PGF2 were generated by incremental additions of each drug to the tissue bath (10E‐10 to 10E‐5 M in all cases). After the maximal dose of stimulator, 10E‐6 M of terbutaline (beta‐2 agonist; tocolytic) was added to the system. Results We found that indeed parous myometrium displays a significantly stronger response to oxytocin than its virgin counterpart (P<0.05). The EC50 of the drug for the receptor appears unchanged, but the maximal response to the drug is higher (P<0.05). Furthermore, the ability of a 10E‐6 M dose of terbutaline to inhibit activation of myometrial strips by maximal doses of oxytocin (10E‐5 M) also differs. Terbutaline inhibits 60±6% of oxytocin‐activated virgin myometrial contraction, vs. 39±5% of oxytocin‐activated parous myometrial contraction (P<0.005). Preliminary ELISA results suggest a ~30% higher expression of oxytocin receptor in non‐pregnant parous uterine tissue. No significant differences in the myometrial dose‐response relationship in virgin versus parous uterine tissue emerged in PGE2 and PGF2 treated strips. Conclusions Our results suggest that at least in the response to oxytocin, parity affects uterine contractility. This supports the general hypothesis that some (likely epigenetic) changes occur in the uterine smooth muscle during pregnancy that persist post‐parturition. Support or Funding Information This study was supported by Midwestern University.