Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis

Guo, Sun‐Wei; Mao, Xiaoyan; Ma, Qingliang; Liu, Xishi

doi:10.1016/j.fertnstert.2012.08.038

Cited by 107 publications

(87 citation statements)

References 69 publications

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“…[45][46][47][48] In particular, elevated myometrial OTR expression is consistent with our recent report that myometrial OTR expression is increased in women with adenomyosis and is positively correlated with the uterine contractility and the severity of dysmenorrhea. 8 The finding that is somewhat novel arising from this study is the increased staining for collagen I and IV, even though our results are consistent with the finding of increased interstitial collagen deposition in CD-1 mice with adenomyosis that was induced exactly the same manner as in our study. 49 Collagen is a fibrous structural protein.…”

Section: Discussionsupporting

confidence: 90%

Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia

et al. 2014

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We have previously reported that induction of adenomyosis in mice results in progressive hyperalgesia, uterine hyperactivity, and elevated plasma corticosterone levels and that epigallocatechin-3-gallate (EGCG) treatment dose dependently suppressed myometrial infiltration and improved generalized hyperalgesia. In this study, we examined whether adenomyosis induced in mice results in the loss of GABAergic inhibition as manifested by the diminished glutamate decarboxylase (GAD) 65-expressing neurons in the brainstem nucleus raphe magnus (NRM) that could correlate with heightened hyperalgesia. We also evaluated whether EGCG treatment would reverse these changes and also improve the expression of some proteins known to be involved in adenomyosis. Adenomyosis was induced in 28 female ICR mice and additional 12 were used as blank controls, as reported previously. At the 16th week, all mice with induced adenomyosis received low-or high-dose EGCG treatment or untreated. Mice without adenomyosis received no treatment. After 3 weeks of treatment, their uterine horns and brains were harvested. The right uterine horn was used for immunohistochemistry analysis and for counting the number of macrophages infiltrating into the ectopic endometrium. The brainstem NRM sections were subjected to immunofluorescence staining for GAD65. We found that mice with induced adenomyosis had significantly diminished GAD65-expressing neurons, concomitant with heightened hyperalgesia. Treatment with EGCG increased these neurons in conjunction with improved hyperalgesia, reduced the expression of pp65, cycloxygenase 2, oxytocin receptor, collagen I and IV, and transient receptor potential vanilloid type 1 in ectopic endometrium or myometrium, reduced the number of macrophages infiltrating into the ectopic endometrium while elevated the expression of progesterone receptor isoform B. Thus, adenomyosis-induced pain resembles neuropathic pain in that there is a remarkable central plasticity.

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Section: Discussionsupporting

confidence: 90%

Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia

et al. 2014

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“…49 It is well documented that uterine contractility of the junctional zone in the nonpregnant uterus is oxytocin dependent. 50 The OTR overexpression may result in uterine hyperperistalsis or dysperistalsis.…”

Section: Discussionmentioning

confidence: 99%

“…9 It is also consistent with our recent report showing increased amplitude, but not frequency, of OTR-mediated uterine contractility in women with adenomyosis. 49 The presence of adenomyosis, in conjunction with the activation of NF-kB, 59 may lead to increased production of proinflammatory cytokines and elevated COX-2 expression, resulting in increased production of PGs. The increased PGs production may ultimately lead to uterine hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Reduces Myometrial Infiltration, Uterine Hyperactivity, and Stress Levels and Alleviates Generalized Hyperalgesia in Mice Induced With Adenomyosis

et al. 2013

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In an effort to search for novel therapeutics for adenomyosis, we sought to determine whether treatment with epigallocatechin-3-gallate (EGCG) would suppress the myometrial infiltration, improve pain behavior, lower stress level, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, which served as a blank control. Starting from 4 weeks after birth, hot plate test was administrated to all mice every 4 weeks. At the 16th week, all mice induced with adenomyosis were randomly divided into 3 groups: low-dose EGCG (5 mg/kg), high-dose EGCG (50 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, the hot plate test was administered again, a blood sample was taken to measure the plasma corticosterone level by enzyme-linked immunosorbent assay, and then all mice were sacrificed. The depth of myometrial infiltration and uterine contractility were also evaluated. We found that the induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and frequency of uterine contractions as well as elevated plasma corticosterone levels. The EGCG treatment dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels. These results suggest that induced adenomyosis causes pain and elevates stress levels in mice. Uterine hyperactivity may contribute to dysmenorrhea in women with adenomyosis who might also have elevated stress level due to pain. The EGCG appears to be a promising compound for treating adenomyosis.

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“…A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 7 Secondary outcomes included menstrual blood loss (MBL) as measured using the menstrual diary. Uterine arteries and intramyometrial blood flow were measured by color Doppler before the start of treatment.…”

Section: Study Outcomesmentioning

confidence: 99%

Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial

Shaaban¹,

Ali²,

Sabra³

et al. 2015

Contraception

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Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis

Cited by 107 publications

References 69 publications

Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia

Possible Loss of GABAergic Inhibition in Mice With Induced Adenomyosis and Treatment With Epigallocatechin-3-Gallate Attenuates the Loss With Improved Hyperalgesia

Epigallocatechin-3-Gallate Reduces Myometrial Infiltration, Uterine Hyperactivity, and Stress Levels and Alleviates Generalized Hyperalgesia in Mice Induced With Adenomyosis

Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial

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