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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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Expression of c-Kit or vimentin immunoreactivity in the reproductive tract.Single confocal optical sections taken from wholemount preparations. As previously reported (Duquette et al., 2005) c-Kit or vimentin immunoreactive cells are present in the myometrium (white arrows) (B & F). However these were rarely observed in the cervix (C & G) and not observed in the vagina (D & H). Studies made for comparative purposes under the same conditions show the well reported extensive network of ICCs (white arrows) present in the stomach (A & E). Scale bar  = 100µm.
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pone-0111307-g005: Expression of c-Kit or vimentin immunoreactivity in the reproductive tract.Single confocal optical sections taken from wholemount preparations. As previously reported (Duquette et al., 2005) c-Kit or vimentin immunoreactive cells are present in the myometrium (white arrows) (B & F). However these were rarely observed in the cervix (C & G) and not observed in the vagina (D & H). Studies made for comparative purposes under the same conditions show the well reported extensive network of ICCs (white arrows) present in the stomach (A & E). Scale bar  = 100µm.

Mentions: We next investigated the presence of c-Kit or vimentin immunoreactive ICs in cervical and vaginal wholemounts. C-Kit-IR cells and vimentin-IR cells were very sparse in the cervix (0.5±0.3, n = 5 and 2.7±0.9, n = 3 cells per field of view; Figure 5C, G). We found no c-Kit-IR (n = 4) or vimentin-IR cells (n = 3) in the vagina (Figure 5D, H). As a positive control, and as has been previously demonstrated [7] (Duquette, Shmygol et al. 2005) c-Kit and vimentin-IR cells were present in the uterus. In our mice, we found 1.2±0.2 (n = 5) c-Kit-IR and 5.7±1.8 (n = 3) vimentin-IR cells labelled per field of view in uterine wholemounts. Importantly these cells did not obviously form a network (Figure 5B, F), unlike the dense networks formed by gastric ICCs from the proximal gastric antrum (Figure 5A, E; also see [40]).


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)

Expression of c-Kit or vimentin immunoreactivity in the reproductive tract.Single confocal optical sections taken from wholemount preparations. As previously reported (Duquette et al., 2005) c-Kit or vimentin immunoreactive cells are present in the myometrium (white arrows) (B & F). However these were rarely observed in the cervix (C & G) and not observed in the vagina (D & H). Studies made for comparative purposes under the same conditions show the well reported extensive network of ICCs (white arrows) present in the stomach (A & E). Scale bar  = 100µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111307-g005: Expression of c-Kit or vimentin immunoreactivity in the reproductive tract.Single confocal optical sections taken from wholemount preparations. As previously reported (Duquette et al., 2005) c-Kit or vimentin immunoreactive cells are present in the myometrium (white arrows) (B & F). However these were rarely observed in the cervix (C & G) and not observed in the vagina (D & H). Studies made for comparative purposes under the same conditions show the well reported extensive network of ICCs (white arrows) present in the stomach (A & E). Scale bar  = 100µm.
Mentions: We next investigated the presence of c-Kit or vimentin immunoreactive ICs in cervical and vaginal wholemounts. C-Kit-IR cells and vimentin-IR cells were very sparse in the cervix (0.5±0.3, n = 5 and 2.7±0.9, n = 3 cells per field of view; Figure 5C, G). We found no c-Kit-IR (n = 4) or vimentin-IR cells (n = 3) in the vagina (Figure 5D, H). As a positive control, and as has been previously demonstrated [7] (Duquette, Shmygol et al. 2005) c-Kit and vimentin-IR cells were present in the uterus. In our mice, we found 1.2±0.2 (n = 5) c-Kit-IR and 5.7±1.8 (n = 3) vimentin-IR cells labelled per field of view in uterine wholemounts. Importantly these cells did not obviously form a network (Figure 5B, F), unlike the dense networks formed by gastric ICCs from the proximal gastric antrum (Figure 5A, E; also see [40]).

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