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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2015 > Volume 64 Number 3 > Lu Yang1), Zhengyu Cao1), Boyang Yu1, 2), and Chengzhi Chai1)

An in vivo mouse model of primary dysmenorrhea

Lu Yang1), Zhengyu Cao1), Boyang Yu1, 2), and Chengzhi Chai1)
1)Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu, P.R.China 2)Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu, P.R.China
Abstract :

Primary dysmenorrhea (PD) is a common gynecological disorder. Hitherto, animal models which recapitulate clinical features of PD have not been fully established. We aimed to examine whether a pain model in mice could mimic the clinic features of PD. After pretreated with estradiol benzoate (1 mg/kg/day) intraperitoneally (i.p.) for 3 consecutive days, non-pregnant female Imprinting Control Region mice (6–8 weeks old) was injected with 0.4 U of oxytocin to induce the stretching or writhing response which was recorded for a time period of 30 min. During the writhing period, the uterine artery blood flow alterations were examined by Doppler ultrasound detection. After writhing test, the uterine morphological changes were observed by hematoxylin and eosin (H&E) staining histopathology. In addition, enzyme-linked immunosorbent assay kit was used to measure the levels of prostaglandins F2α/prostaglandins E2 (PGF2α/PGE2) and TXB2 (a metabolite of TXA2)/6-keto-PGF1α (a metabolite of PGI2) in the uterine tissue homogenates and plasma, respectively. Western blot analyses were performed to determine the expressions of oxytocin receptor (OTR), beta2-adrenergic receptor (beta2-AR), and cyclooxygenase-2 (COX-2) in uterine, which are responsible for the uterine contraction. The writhing response only occurred in the estrogen pretreated female mice. The area of uterine myometrium significantly decreased along with the increased thickness in the oxytocininduced estrogen pretreated mice model. The uterine artery blood flow velocity dropped, while the pulsatility index and resistance index slightly increased after the injection of oxytocin. The PGF2α/ PGE2 level significantly increased and the plasma TXB2/6-keto-PGF1α level significantly enhanced. Compared with the control group, the uterine histopathology demonstrated moderate to severe edema of endometrium lamina propria. In consistent with the uterine morphological changes, a significant reduction of beta2-AR and a significant increase of OTR and COX-2 in the uterine tissue were observed. The writhing response was caused by the abnormal contraction of uterus. The uterine spasm and ischemia changes of oxytocin-induced estrogen pretreated female mice model were similar to the pathology of human PD. We reported an in vivo mice model, which can be used to study PD and for clinical therapeutic evaluations

Keywords :
: in vivo animal model, primary dysmenorrhea, uterine pathological change, uterine artery blood flow, uterine contraction

Date Deposited : 07 Jan 2016 10:42

Last Modified : 07 Jan 2016 10:42

Official URL: http://

Volume 64, Number 3, April 2015 , ISSN 295–303

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