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Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

Gravina FS, van Helden DF, Kerr KP, de Oliveira RB, Jobling P - PLoS ONE (2014)

Bottom Line: ICs were found in small numbers in the mouse cervix but not in the vagina.Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active.Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, The University of Newcastle, Callaghan, NSW, Australia.

ABSTRACT

Background/aims: The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking.

Methodology/principal findings: Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina.

Conclusions/significance: Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

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Tension recordings from cervical and vaginal strips of smooth muscle held at 5 mN resting tension in PSS with uterine data obtained from longitudinal muscle strips presented for comparative purposes.Non-pregnant (A) and late pregnant (D) mice uteri exhibited spontaneous contractions. The cervices from non-pregnant mice (B) exhibited spontaneous contractions in estrus and metestrus, but not diestrus and proestrus (see figure 3 for more details); while cervices from pregnant mice (E) always exhibited spontaneous contractions. Vaginal tissues from non-pregnant (C) and pregnant (F) mice were generally not spontaneously active.
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pone-0111307-g002: Tension recordings from cervical and vaginal strips of smooth muscle held at 5 mN resting tension in PSS with uterine data obtained from longitudinal muscle strips presented for comparative purposes.Non-pregnant (A) and late pregnant (D) mice uteri exhibited spontaneous contractions. The cervices from non-pregnant mice (B) exhibited spontaneous contractions in estrus and metestrus, but not diestrus and proestrus (see figure 3 for more details); while cervices from pregnant mice (E) always exhibited spontaneous contractions. Vaginal tissues from non-pregnant (C) and pregnant (F) mice were generally not spontaneously active.

Mentions: Cervical tissues from nearly half the non-pregnant mice were spontaneously active (47% active, n = 17, Figure 2B), while cervical tissues from all late pregnant mice showed spontaneous contractions (n = 48, Figure 2E). By comparison, uterine tissues always exhibited spontaneous contractions, when obtained from either non-pregnant (n = 17, Figure 2A) or late pregnant mice (19 days gestation, n = 9, Figure 2D). Contractions in both the active cervix and uterus were reasonably stable, the 60/30 min frequency and amplitude ratios (5 min sampling) being 0.76±0.12 and 0.78±0.24 (n = 3) respectively for the cervix and 0.82±0.15 and 0.93±0.17 (n = 7) respectively for the uterus. Uterine tissues obtained from mice in middle pregnancy (14 days) were quiescent (n = 2, data not shown). Vaginal tissues were almost never spontaneously active (1 of 22 vaginal strips, Figure 2C, F).


Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

Gravina FS, van Helden DF, Kerr KP, de Oliveira RB, Jobling P - PLoS ONE (2014)

Tension recordings from cervical and vaginal strips of smooth muscle held at 5 mN resting tension in PSS with uterine data obtained from longitudinal muscle strips presented for comparative purposes.Non-pregnant (A) and late pregnant (D) mice uteri exhibited spontaneous contractions. The cervices from non-pregnant mice (B) exhibited spontaneous contractions in estrus and metestrus, but not diestrus and proestrus (see figure 3 for more details); while cervices from pregnant mice (E) always exhibited spontaneous contractions. Vaginal tissues from non-pregnant (C) and pregnant (F) mice were generally not spontaneously active.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206458&req=5

pone-0111307-g002: Tension recordings from cervical and vaginal strips of smooth muscle held at 5 mN resting tension in PSS with uterine data obtained from longitudinal muscle strips presented for comparative purposes.Non-pregnant (A) and late pregnant (D) mice uteri exhibited spontaneous contractions. The cervices from non-pregnant mice (B) exhibited spontaneous contractions in estrus and metestrus, but not diestrus and proestrus (see figure 3 for more details); while cervices from pregnant mice (E) always exhibited spontaneous contractions. Vaginal tissues from non-pregnant (C) and pregnant (F) mice were generally not spontaneously active.
Mentions: Cervical tissues from nearly half the non-pregnant mice were spontaneously active (47% active, n = 17, Figure 2B), while cervical tissues from all late pregnant mice showed spontaneous contractions (n = 48, Figure 2E). By comparison, uterine tissues always exhibited spontaneous contractions, when obtained from either non-pregnant (n = 17, Figure 2A) or late pregnant mice (19 days gestation, n = 9, Figure 2D). Contractions in both the active cervix and uterus were reasonably stable, the 60/30 min frequency and amplitude ratios (5 min sampling) being 0.76±0.12 and 0.78±0.24 (n = 3) respectively for the cervix and 0.82±0.15 and 0.93±0.17 (n = 7) respectively for the uterus. Uterine tissues obtained from mice in middle pregnancy (14 days) were quiescent (n = 2, data not shown). Vaginal tissues were almost never spontaneously active (1 of 22 vaginal strips, Figure 2C, F).

Bottom Line: ICs were found in small numbers in the mouse cervix but not in the vagina.Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active.Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, The University of Newcastle, Callaghan, NSW, Australia.

ABSTRACT

Background/aims: The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking.

Methodology/principal findings: Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina.

Conclusions/significance: Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

Show MeSH
Related in: MedlinePlus