Name: intrauterine telemetry to measure mouse contractile pressure in vivo
Uploaded: 2015-04-06T15:00:00
Description: Watch this Scientific Journal Video about Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo at JoVE.com

This work was supported by funding from the March of Dimes FY12-133 (S.K.E.) and the National Institutes of Health R01HD037831 (S.K.E.). We would like to thank Dr. Deborah Frank for critical review of the manuscript.

NOTE: All animal procedures complied with guidelines for the care and use of animals set forth by the National Institutes of Health. All protocols were approved by the Animal Studies Committee at Washington University in St. Louis. 
NOTE: Specific materials and equipment for this protocol are listed Materials and Equipment table.
1. Timed Breeding of Female Mice
<ol>
	<li>Breed adult females between two and six months of age in a 2 hr time window with males. Specific breeding hr are not...

<ol>
	<li>Slattery, M. M., Morrison, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preterm+delivery.">Preterm delivery.</a> Lancet. 360, 1489-1497 (2002).</li><li>Goldenberg, R. L., Culhane, J. F., Iams, J. D., Romero, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+and+causes+of+preterm+birth.">Epidemiology and causes of preterm birth.</a> Lancet. 371, 75-84 (2008).</li><li>Keelan, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacological+inhibition+of+inflammatory+pathways+for+the+prevention+of+preterm+birth.">Pharmacological inhibition of inflammatory pathways for the prevention of preterm birth.</a> Journal Of Reproductive Immunology. 88, 176-184 (2011).</li><li>Voltolini, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+spontaneous+preterm+birth:+from+underlying+mechanisms+to+predictive+and+preventive+interventions.">Understanding spontaneous preterm birth: from underlying mechanisms to predictive and preventive interventions.</a> Reproductive Sciences. 20, 1274-1292 (2013).</li><li>Ratajczak, C. K., Muglia, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Insights+into+parturition+biology+from+genetically+altered+mice.">Insights into parturition biology from genetically altered mice.</a> Pediatric research. 64, 581-589 (2008).</li><li>Rajakumar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Placental+HIF-1+alpha,+HIF-2+alpha,+membrane+and+soluble+VEGF+receptor-1+proteins+are+not+increased+in+normotensive+pregnancies+complicated+by+late-onset+intrauterine+growth+restriction.">Placental HIF-1 alpha, HIF-2 alpha, membrane and soluble VEGF receptor-1 proteins are not increased in normotensive pregnancies complicated by late-onset intrauterine growth restriction.</a> American Journal Of Physiology. Regulatory, Integrative And Comparative Physiology. 293, (2007).</li><li>Whitesall, S. E., Hoff, J. B., Vollmer, A. P., D'Alecy, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+simultaneous+measurement+of+mouse+systolic+arterial+blood+pressure+by+radiotelemetry+and+tail-cuff+methods.+American+journal+of+physiology.">Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods. American journal of physiology.</a> Heart And Circulatory Physiology. 286, H2408-H2415 (2004).</li><li>Mackay, L. B., Shi, L. B., Maul, H. .., Maner, W. L., Garfield, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+bilateral+pelvic+neurectomy+on+cervical+ripening+in+pregnant+rats.">The effect of bilateral pelvic neurectomy on cervical ripening in pregnant rats.</a> Journal Of Perinatal Medicine. 37, 263-269 (2009).</li><li>Pierce, S. L., Kutschke, W., Cabeza, R., England, S. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+measurement+of+intrauterine+pressure+by+telemetry:+a+new+approach+for+studying+parturition+in+mouse+models.">In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models.</a> Physiol Genomics. 42, 310-316 (2010).</li><li>Imamura, T., Luedke, C. E., Vogt, S. K., Muglia, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxytocin+modulates+the+onset+of+murine+parturition+by+competing+ovarian+and+uterine+effects.">Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects.</a> American Journal Of Physiology. Regulatory, Integrative And Comparative Physiology. 279, R1061-R1067 (2000).</li><li>McCloskey, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+inwardly+rectifying+K++channel+KIR7.1+controls+uterine+excitability+throughout+pregnancy.">The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy.</a> EMBO Mol Med. 6 (9), 1161-1174 (2014).</li></ol>

Investigations of myometrial contractility have relied on ex vivo measurements of muscle tension. This methodology can be useful for early-stage testing of newly developed uterotonic drugs that cannot be administered to live animals. However, in vivo approaches are necessary to longitudinally understand the progression of labor. The in vivo measurements serve several purposes. First, they enable capture of a complete picture of changes in uterine contractile pattern over the duration of pregnan...

Preterm birth is the leading cause of perinatal morbidity and mortality in developed countries; it is responsible for 50% of perinatal morbidity and 75% of perinatal mortality1,2. Preterm labor is multifaceted and can be idiopathic. Although much research has emerged on the molecular and electrical pathways transforming the myometrium from a quiescent tissue into a contractile one, the exact pathophysiology of preterm labor remains elusive. Endocrine, inflammatory, and gene regulation have all been linked to preterm labor3,4. However, ethical concerns limit the ability to conduct research on the mechanisms of preterm labor in humans.
Given these limitations, many researchers have turned to mice as a model system with which to study the physiology of parturition. Mice have short gestations lasting approximately three weeks and can be easily genetically manipulated. Additionally, multiple genetic mouse models have been developed to determine the signaling pathways that are essential for labor5. Despite key differences between mouse and human parturition, mice and humans share many of the same mechanisms that are essential for labor, including intrauterine inflammation and infection6. Thus, mice serve as an invaluable tool for examining uterine activity. To date, the gold standard to measure uterine contractility in mice has been ex vivo isometric tension recordings; however, this is limited to one gestational time point per experiment and requires removal of the uterus from its physiological environment. Another important factor is the large number of animals required for these investigations. Lastly, this methodology does not allow for longitudinal studies examining induction of labor and preterm pathophysiology.
Recent advancements made in radiometric telemetry devices used to study arterial pressure changes7 in mice and intrauterine pressure in rats8 begged the question to whether the same technology could be used to study changes in intrauterine pressure in mice during pregnancy. After initial troubleshooting, a method was successfully developed to measure labor induction and progression in a mouse. This in vivo approach can measure the transition from the low-pressure state of the quiescent uterus to the high-pressure state indicative of forceful labor contractions. This method has also been able to detect significant pressure differences between transgenic mice with compromised parturition and wild type mice, demonstrating the physiological impact of gene expression9. This protocol provides a real-time, in vivo method to study mouse uterine pressure during pregnancy.

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			<td>Specialized for rodents</td>
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			<td>Fibre optic gooseneck external light source</td>
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			<td height="42" style="height:42px;width:245px;">PhysioTel PA-C10 Pressure Transmitter</td>
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			<td style="width:105px;">&#160;Data Sciences International</td>
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			<td height="42" style="height:42px;width:245px;">Dataquest ART 4.3.2 Analysis Platinum</td>
			<td style="width:105px;">&#160;Data Sciences International</td>
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			<td>Analysis software</td>
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			<td>Purified Soft Diet for Rodents</td>
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			<td style="width:105px;">Sigma-Aldrich</td>
			<td>Z273287</td>
			<td>Enzyme detergent</td>
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intrauterine telemetry to measure mouse contractile pressure in vivo

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor.

Real-time in vivo intrauterine pressures can be recorded by using a telemetric acquisition system. Pressure sampling paired with simultaneous video recording of the mouse was used to capture the exact time of each pup&#8217;s delivery and correlate delivery time to the intrauterine pressure of the mother. All the data points can then be plotted throughout the recording to generate a pressure-versus-time plot (Figure 1A). This plot shows the points during gestation when the intrauterine pressure ...

Watch this Scientific Journal Video about Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo at JoVE.com

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

This manuscript provides a protocol for implanting telemeters in the mouse for the purpose of measuring intrauterine pressures during pregnancy.

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. ...

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