Objective Our overall hypothesis is that pregnancy’s mechanical and hormonal stimuli induce permanent changes in the properties of uterine tissue. Our objective here was to quantify the variation in the response to oxytocin, PGE2, and PGF2α of myometrium from pregnant female rats at term, during labor, and during involution. Method First time (Preg1) and second time (Preg2) pregnant female 18 weeks old rats were euthanized either at term (day 22 of gestation, no labor E22), during labor (day 22 of gestation after birth of first pup, E22L), or at involution (2 days after parturition, INV). For each group, 8 rats were used. Six 3×10 mm myometrial strips were suspended in a tissue bath containing Krebs solution (in mM, NaCl 117, KCl 4.7, NaHCO3 25, MgCl2 1.2, KH2PO4 1.2, CaCl2 2.5, glucose 11, pH= 7.4) at 37°C and bubbled with 95% O2 and 5% CO2. Separate dose responses curves to the endogenous uterotonics 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). Results In E22 tissue, the affinity of oxytocin for its receptor changes somewhat significantly (P= 0.042) between Preg1 (log EC50 −8.53 ± 0.07) and Preg2 (log EC50 −8.72 ± 0.07), while the maximal response to the drug was essentially the same (P<0.05). In E22L tissue, oxytocin log EC50 is similar in Preg1 and Preg2, while maximal response was higher in Preg1 than in Preg2 tissue, (Max for Preg1= 0.97 ± 0.03; Max for Preg2= 0.73 ± 0.06 AUC/AUC KCl, P<0.001). During INV, no differences in log EC50 or Max response were detected (P<0.05). For PGE2, in E22, no significant difference was detected in log EC50 between Preg1 and Preg2. However, maximal response was higher in Preg1 than Preg2 (Max for Preg1= 0.37 ± 0.02; Max for Preg2= 0.28 ± 0.01 AUC/AUC KCl, P=0.012). The same is true for E22L (Max for Preg1= 0.43 ± 0.03; Max for Preg2= 0.33 ± 0.02 AUC/AUC KCl, P=0.018). In INV, instead, the log EC50 was higher for Preg1 than Preg2 (log EC50 for Preg1 −7.52 ± 0.4; log EC50 for Preg1 −6.35 ± 0.1; P=0.006), while the maximal response was stronger in Preg2 than in Preg1 (Max for Preg1= 0.12 ± 0.02; Max for Preg2= 0.28 ± 0.01 AUC/AUC KCl; P<0.001). For PGF2, in E22, logEC50 is similar in Preg1 and Preg2, while Preg2 showed a stronger response than Preg1 (Max for Preg1= 0.48 ± 0.02; Max for Preg2= 0.61 ± 0.02 AUC/AUC KCl; P<0.001) A similar pattern was demonstrated in E22L (Max for Preg1= 0.30 ± 0.01; Max for Preg2= 0.35 ± 0.01 AUC/AUC KCl; P=0.019). Finally, in INV, log EC50 was higher in Preg1 than Preg2 (log EC50 for Preg1= −7.01± 0.09; log EC50 for Preg1 −6.22 ± 0.0.09; P<0.001), but the maximal response was moderately stronger in Preg2 than in Preg1 (Max for Preg1= 0.44 ± 0.01; Max for Preg2= 0.48 ± 0.01 AUC/AUC KCl; P=0.03). Conclusions In the past, we demonstrated alteration in the response of never before pregnant and proven breeder myometrial tissues to endogenous uterotonic agents in the non‐pregnant and pregnant state. Our current results show that also at term, during labor, and during ...
ObjectiveDuring pregnancy, hormonal and mechanical stimuli induce profound changes in the uterus. Involution reverses these changes during the postpartum period. Epidemiological studies have shown that parity is associated with increased intensity of postpartum contractions and risk for uterine atony, and decreased incidence in dysmenorrhea and fibroids. Thus, we hypothesize that an epigenetic memory of pregnancy is preserved in in the myometrium, the smooth muscle component of the uterus. To test this hypothesis, we conducted motility studies on myometrial strips from non‐pregnant (NP) and pregnant Sprague‐Dawley (Charles River) rats (P).MethodsVirgin (V) and proven breeders (PB) female non‐pregnant 18 week old rats were euthanized during proestrus. First time (Preg1) and second time (Preg2) pregnant female 18 week old rats were euthanized on day 20 of a 22 day pregnancy. The uterine horns were extracted, dissected longitudinally, and the content and lining of the uterus were removed. One horn was dissected into six 3×10 mm strips, which were then suspended in a tissue bath containing Krebs solution (in mM, NaCl 117, KCl 4.7, NaHCO3 25, MgCl2 1.2, KH2PO4 1.2, CaCl2 2.5, glucose 11, pH= 7.4) at 37°C and bubbled with 95% O2 + 5% CO2. Separate dose response curves to the endogenous uterotonics oxytocin, PGE2, and PGF2α were generated by incremental additions of each drug to the tissue bath (10E‐10 to 10E‐5 M in all cases). Contractility was expressed as area under the curve (AUC) normalized to AUC in the presence of 40 mM KCl (AUC/AUC KCl). Data are mean ± SE.ResultsIn non‐pregnant tissue (12 rats/group), the affinity of oxytocin for its receptor did not change significantly (P<0.05) between V and PB, but the maximal response to the drug was higher in PB (Max for V= 0.756 ± 0.001; Max for PB= 0.905 ± 0.002 AUC/AUC KCl, P<0.001). In P tissue, EC50 was similar in Preg1 and Preg2 and significantly higher than in NP myometrium (logEC50 in NP PB= −8.44 ± 0.02; logEC50 in P Preg2= −8.9 ± 0.2 M, P=0.03). Maximal response was similar in Pre1 and Preg2 tissue, but significantly reduced compared to PB tissue (Max for Pre1= 0.57 ± 0.02; Max for PB= 0.59 ± 0.03 AUC/AUC KC, P<0.001). For PGE2, EC50 and Max were not significantly different in V and PB. However, in pregnancy, Preg2 tissue displayed higher affinity for PGE2 than Preg1 tissue (logEC50 in Preg1= −6.1 ± 0.01; logEC50 in Preg2= −6.3 ± 0.01 M, P=0.037), while maximal response remained unchanged. Dose response to PGF2 in NP myometrium revealed both higher affinity (P=0.022) and higher maximal response (P=0.02) in V than in PB (logEC50 in V= −6.49 ± 0.07; logEC50 in PB= −6.2 ± 0.1 M; Max for V= 0.44 ± 0.02; Max for PB= 0.33 ± 0.02 AUC/AUC KCl). This trend was partially reversed in P myometrium (logEC50 in Preg1= −5.72 ± 0.08; logEC50 in Preg2= −5.77 ± 0.08 M, P>0.05; Max for Preg1= 0.30 ± 0.01; Max for Preg2= 0.35 ± 0.02 AUC/AUC KCl, P<0.05).ConclusionsOur results confirm that the myometrial response to endogenous uterotonic agents is altered after the first pregnancy. Understanding the mechanisms underlying these differences is an important first step toward explaining the impact of pregnancy in subsequent uterine function.Support or Funding InformationThis study was funded by a MWU intramural grant to MP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.