Microelectrode array analysis of mouse uterine smooth muscle electrical activity†

Abstract

Uterine contractions are important for various functions of the female reproductive cycle. Contractions are generated, in part, by electrical coupling of smooth muscle cells of the myometrium, the main muscle layer of the uterus. Aberrant myometrial electrical activity can lead to uterine dysfunction. To better understand and treat conditions associated with aberrant activity, it is crucial to understand the mechanisms that underlie normal activity. Here, we used microelectrode array (MEA) to simultaneously record and characterize myometrial electrical activities at high spatial and temporal resolution. Mouse myometrial longitudinal muscle tissue was isolated at different stages throughout the estrous cycle and placed on an 8×8 MEA. Electrical activity was recorded for 10 min at a sampling rate of 12.5 kHz. We used a spike-tracking algorithm to independently analyze each channel and developed a pipeline to quantify the amplitude, duration, frequency, and synchronicity of the electrical activities. Electrical activities in estrous were more synchronous, and had shorter duration, higher frequency, and lower amplitude than electrical activities in non-estrous. We conclude that MEA can be used to detect differential patterns of myometrial electrical activity in distinct estrous cycle stages. In the future, this methodology can be used to assess different physiological and pathological states and evaluate therapeutic agents that regulate uterine function.

Mapping uterine calcium dynamics during the ovulatory cycle in live mice

“…Furthermore, electrodes primarily report the activity of the cells they contact, and may be less sensitive or insensitive to activity in a different muscle layer. Microelectrode arrays provided in-layer spatial resolution and showed that estrus explants fired more synchronously than diestrus explants (11), consistent with the stage-dependent differences in event velocity we reported.…”

“…Tension measurements on explants from mice showed a dominant oviductal site in all stages except metestrus, slower propagation speeds in estrus and diestrus than in proestrus and metestrus, and diestrus as the most quiescent phase (Dodds et al, 2015). In dissected sheets of mouse longitudinal muscle, estrous samples had firing that was shorter, higher frequency, lower amplitude, and more synchronous than non-estrous samples (Ma et al, 2020), perhaps indicative of rapid but weak electrical activity during estrous.…”

Mode Switch of Ca2 + Oscillation-Mediated Uterine Peristalsis and Associated Embryo Implantation Impairments in Mouse Adenomyosis

“…This study points to several future lines of investigation on uterine peristalsis in the non-pregnant uterus, a research area that has been neglected, yet is of clinical importance (Ma et al, 2020;Ivell and Anand-Ivell, 2021). A straight-forward and obvious investigation would study the molecular basis underlying the mode switch of uterine Ca 2+ oscillations and peristalsis.…”

Modeling and experimental approaches for elucidating multi-scale uterine smooth muscle electro- and mechano-physiology: A review

“…Since then, many investigators have used electrodes to measure uterine electrical activity. The protocol varies depending on if the experiment is conducted ex vivo (Lammers et al, 1994;Ma et al, 2020) or in vivo (Kao, 1959;. For ex vivo experiments, typically one of the uterine horns from small laboratory animals is excised and either kept intact (Csapo and Takeda, 1965;Lammers et al, 2008), opened along the mesometrial or anti-mesometrial border (Lammers et al, 2015;Lutton et al, 2018), or dissected to extract smaller segments of the myometrium (Landa et al, 1959;Kuriyama and Suzuki, 1976).…”

“…There are few studies investigating the influence of the estrus cycle (diestrus/estrus) or during early pregnancy. Recently, Ma et al identified patterns of coordinated activity in estrus and diestrus mice (Ma et al, 2020). They used a microelectrode array of 64 electrodes with an inter-electrode distance of 200 μm.…”