In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models

Abstract

Pierce SL, Kutschke W, Cabeza R, England SK. In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models. Physiol Genomics 42: 310 -316, 2010. First published May 11, 2010 doi:10.1152/physiolgenomics.00058.2010.-Transgenic and knockout mouse models have proven useful in the study of genes necessary for parturition-including genes that affect the timing and/or progression of labor contractions. However, taking full advantage of these models will require a detailed characterization of the contractile patterns in the mouse uterus. Currently the best methodology for this has been measurement of isometric tension in isolated muscle strips in vitro. However, this methodology does not provide a real-time measure of changes in uterine pressure over the course of pregnancy. Recent advances have opened the possibility of using radiotelemetric devices to more accurately and comprehensively study intrauterine pressure in vivo. We tested the effectiveness of this technology in the mouse, in both wild-type (WT) mice and a mouse model of defective parturition (SK3 channel-overexpressing mice), after surgical implant of telemetry transmitters into the uterine horn. Continuous recordings from day 18 of pregnancy through delivery revealed that WT mice typically deliver during the 12-h dark cycle after 19.5 days postcoitum. In these mice, intrauterine pressure gradually increases during this cycle, to threefold greater than that measured during the 12-h cycle before delivery. SK3-overexpressing mice, by contrast, exhibited lower intrauterine pressure over the same period. These results are consistent with the outcome of previous in vitro studies, and they indicate that telemetry is an accurate method for measuring uterine contraction, and hence parturition, in mice. The use of this technology will lead to important novel insights into changes in intrauterine pressure during the course of pregnancy. potassium channel; SK3 channel-overexpressing mice; preterm labor; uterine contraction; myometrium PRETERM DELIVERIES alone account for over 12.6% of all births in the U.S. and are associated with a high percentage (ϳ85%) of perinatal morbidity and mortality (2). Despite increased medical intervention over the past 30 years, preterm birth rates have risen by 28%-with most of these births occurring in women who do not have any of the known risk factors. Risk factors that have been identified are related to four distinct processes, each of which activates multiple signaling pathways and leads to preterm birth: precocious fetal endocrine activation, uterine overdistension, decidual bleeding, and intrauterine inflammation/infection (14).Genetically modified mouse models have served as effective systems in which to investigate the signaling pathways essential to labor-both preterm and term. Despite certain differences in parturition between human and mouse, these species are similar with respect to many of the pathways that are known to modify pregnancy outcome (8). Mouse models of alte...

CyPPA, a positive modulator of small-conductance Ca2+-activated K+ channels, inhibits phasic uterine contractions and delays preterm birth in mice

“…To directly evaluate its potential in preterm labor intervention, we administered CyPPA only after consistent signs of labor had begun, 11 h after RU486 injection (T11). This time point correlates with a distinct increase in intrauterine pressure as reported by Pierce and colleagues (26). In the 13-h experimen- tal treatment window assessed (T11-T24), CyPPA significantly delayed parturition by an average of 3.4 h and increased the number of pups retained in the uterus over 2.5-fold.…”

“…Here, we specifically assessed the ability of CyPPA to delay preterm parturition in mice induced with the progesterone receptor antagonist RU486. This method reliably induced preterm birth because 100% of control (RU486 ϩ vehicle) animals delivered within 20 h of injection, concordant with previous studies utilizing this model (8,11,18,25,26). We employed DPC 16 mice since induction at earlier gestation times was associated with pup resorption in pilot studies.…”

“…Appreciation for the functional influence of these channels is derived largely from studies of the conditional K Ca 2.3-overexpressing (SK3 T/T ) mouse. In this model, mice exhibit drastically impaired uterine contraction magnitude, compromised parturition, and protection from induced preterm labor, all of which are corrected or prevented by antibiotic-driven K Ca 2.3 downregulation (4,7,25,26). Since targeted genetic manipulation of channel expression is not presently a feasible approach for acute clinical intervention, the current study addressed whether native myometrial K Ca 2 channels might be exploited pharmacologically to amplify their functional impact and promote uterine quiescence, particularly during pregnancy.…”

Single-Nucleotide Polymorphisms in the KCNN3 Gene Associate With Preterm Birth

“…This is likely a result of the hyperpolarizing potential of the SK3 channel, which maintains the myometrial cells in a hypoexcitable state. Overexpression of the hyperpolarizing SK3 channel in mice results in attenuated myometrial contractions leading to inefficient labor 9,16. Based on this mouse studies, we sought to determine whether the converse is true whereby polymorphisms in this channel would associate with PTB.…”

Three-Dimensional High-Frequency Ultrasonography for Early Detection and Characterization of Embryo Implantation Site Development in the Mouse

“…[26, 27], ultrasounds before the invasive procedure allows researchers to confirm viable pregnancies prior to subjecting the mouse to surgery. Furthermore, ultrasounds after the procedure provide reassurance that the pups have remained viable.…”