The Establishment of a Mouse Model of Recurrent Primary Dysmenorrhea

Abstract

Primary dysmenorrhea is one of the most common reasons for gynecologic visits, but due to the lack of suitable animal models, the pathologic mechanisms and related drug development are limited. Herein, we establish a new mouse model which can mimic the periodic occurrence of primary dysmenorrhea to solve this problem. Non-pregnant female mice were pretreated with estradiol benzoate for 3 consecutive days. After that, mice were injected with oxytocin to simulate menstrual pain on the 4th, 8th, 12th, and 16th days (four estrus cycles). Assessment of the cumulative writhing score, uterine tissue morphology, and uterine artery blood flow and biochemical analysis were performed at each time point. Oxytocin injection induced an equally severe writhing reaction and increased PGF2α accompanied with upregulated expression of COX-2 on the 4th and 8th days. In addition, decreased uterine artery blood flow but increased resistive index (RI) and pulsatility index (PI) were also observed. Furthermore, the metabolomics analysis results indicated that arachidonic acid metabolism; linoleic acid metabolism; glycerophospholipid metabolism; valine, leucine, and isoleucine biosynthesis; alpha-linolenic acid metabolism; and biosynthesis of unsaturated fatty acids might play important roles in the recurrence of primary dysmenorrhea. This new mouse model is able to mimic the clinical characteristics of primary dysmenorrhea for up to two estrous cycles.

The therapeutic mechanism of Curcumae Radix against primary dysmenorrea based on 5-HTR/Ca2+/MAPK and fatty acids metabolomics

“…When the proportion of n6/n3 increased, the proliferation and metastasis of tumor cells were mediated, inflammation and thrombosis were promoted, and the concentration of C20:4n6 and PGs in the ovaries of female rats was significantly increased. These substances were also closely related to PD, indicating that the ratio of n6/n3 was related to PD ( Yi et al, 2012 ; Zhang et al, 2021 ; Hong et al, 2022 ). CW significantly decreased the n6/n3 ratio in the liver ( p < 0.001), indicating that it was able to alleviate the symptoms of PD by improving the FA metabolic pathway ( Figure 5 ).…”

“…To further investigate the mechanism of CW in the treatment of PD, in vivo pharmacodynamic experiments were continued and also corroborated the results of in vitro pharmacodynamic experiments. Pathological tissue sections and biochemical factors such as PGE 2 are commonly used to assess PD progression ( Sharghi et al, 2019 ; Zhang et al, 2021 ; Arabnezhad et al, 2022 ; Hong et al, 2022 ). Histopathological changes in the uteri of PD rats usually include uterine wall thinning, structural disorders, glandular abnormalities, marked hyperplasia, and inflammatory cell infiltration ( Tong et al, 2021 ).…”

“…NO is produced by arginine under the action of nitric oxide synthase, relaxes uterine smooth muscle cells, dilates blood vessels, and has an analgesic effect. AA mediates the production of inflammatory mediators through COX-2 catalysis, which is a synthetic substrate of PGF 2α and PGE 2 , induces platelet aggregation, and regulates smooth muscle contraction and the production of inflammatory cytokines ( Zhang et al, 2021 ; Hong et al, 2022 ).…”

N-3 polyunsaturated fatty acids (PUFAs) and physical exercise have the potential to reduce pain intensity in women with primary dysmenorrhea: Systematic Review

“…Primary dysmenorrhea is caused by uterine contractility and hypersecretion of prostaglandins, especially F2 Alpha (PGF2-a) when women are menstruating (Barcikowska et al 2022;Romero-Morales et al 2020;Hong et al 2022). Primary dysmenorrhea is menstrual pain that arises and is felt in the absence of organic disease (Bernardi et al 2017;Abreu-Sánchez et al 2020).…”

Editorial of Special Issue ‘Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection’

“…Characterizing preclinical animal models simulating human diseases is an essential step for bench-to-bed translation research [24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Mendes-Pinheiro and colleagues studied the behavioral domains of 6-hydroxydopamine (6-OHDA)-induced mouse model of PD.…”