Monitoring uterine contractility in mice using a transcervical intrauterine pressure catheter

Abstract

In mouse models used to study parturition or pre-clinical therapeutic testing, measurement of uterine contractions is limited to either isometric tension or operative intrauterine pressure (IUP). The goal of this study was to: (1) develop a method for transcervical insertion of a pressure catheter to measure intrauterine contractile pressure during mouse pregnancy, (2) determine whether this method can be utilized numerous times in a single mouse pregnancy without affecting the timing of delivery or fetal outcome and (3) compare the contractile activity between mouse models of term and preterm labor (PTL). Visualization of the cervix allowed intrauterine pressure catheter (IUPC) placement into anesthetized pregnant mice (plug = day 1, delivery = day 19.5). The amplitude, frequency, duration and area under the curve (AUC) of IUP was lowest on days 16-18, increased significantly ( < 0.05) on the morning of day 19 and reached maximal levels during by the afternoon of day 19 and into the intrapartum period. An AUC threshold of 2.77 mmHg discriminated between inactive labor (day 19 am) and active labor (day 19 pm and intrapartum period). Mice examined on a single vs every experimental timepoint did not have significantly different IUP, timing of delivery, offspring number or fetal/neonatal weight. The IUP was significantly greater in LPS-treated and RU486-treated mouse models of PTL compared to time-matched vehicle control mice. Intrapartum IUP was not significantly different between term and preterm mice. We conclude that utilization of a transcervical IUPC allows sensitive assessment of uterine contractile activity and labor progression in mouse models without the need for operative approaches.

Intrauterine Pressures Adjusted by Reichert’s Membrane Are Crucial for Early Mouse Morphogenesis

“…Disturbance of intrauterine contractions at the preimplantation stage causes the aberrant distribution of implanted embryos (Chen et al, 2011). At the end of embryogenesis, uterine muscle contractions deliver embryos, which is also known as labor (Rada et al, 2015;Robuck et al, 2018). Inappropriate uterine muscle contractions cause preterm or delayed labor (Pierce et al, 2008(Pierce et al, , 2010Bond et al, 2000;Padol et al, 2017).…”

“…Previously, we have shown that physical confinement mimicking the uterine environment is crucial to elongation into an egg-cylinder shape (Hiramatsu et al, 2013). Although uterine smooth muscle exerts intrauterine pressures, otherwise known as labor, at delivery in the late stage of a mouse pregnancy (Pierce et al, 2010;Grotegut et al, 2016;Rada et al, 2015;Robuck et al, 2018), its effects during early implantation stages remain unexplored. To address how much mechanical stress is exerted on embryos in utero, we directly measured intrauterine pressures at peri-implantation stages by inserting a microtransducer-mounted catheter into intrauterine space through one side of exposed uterine horn (Figure 5D).…”

“…We found that intrauterine pressures of non-pregnant uteri were periodically detected due to smooth muscle contraction and relaxation (Figure 5E, NP). Intrauterine pressure curves were evaluated with amplitude, an average contractile integral (AUC), frequency, duration and Montevideo units, following previously described methods (Robuck et al, 2018) (Figure 5F). After fertilization from E3.5 to E6.5, the amplitude, AUC, frequency, and Montevideo units were increased compared with those of (P-R) Representative sagittal (P and P 0 ) and transverse views (Q and R) of a Lama1 À/À embryo and Lama1 +/À decidua with micro-CT at E6.5.…”

“…To exclude the possibility that our approach in measuring intrauterine pressures within decidua disrupts normal values, we also examined intrauterine pressures in a relatively noninvasive transcervical manner (Figures S4A and S4B; Robuck et al, 2018). We compared the amplitude measured with an abdominal operation through an exposed uterine horn to that with a transcervical protocol through the vagina at E6.5 and found that these two amplitudes did not significantly differ (Figures S4A-S4C).…”

“…Baseline (0 mmHg) was adjusted in PBS prior to the insertion of the catheter into uterine tissue, including decidua compression and uterine muscle contraction, at each embryonic stage. The whole intrauterine pressure, involving uterine contractions exerted on decidua, was assessed by previously described methods (Robuck et al, 2018): mean amplitude and frequency, area under the curve (AUC) and Montevideo units (the sum of amplitudes during a 10 minute period of time).…”