Systemic changes in a mouse model of VCD-induced premature ovarian failure

Cao, Lian Bao; Leung, Chi-Wai; Law, Patrick Wai-Nok; Lv, Yue; Ng, Cheuk-Hei; Liu, Hong Bin; Lü, Gang; Jin, Long; Chan, Wai Yee

doi:10.1016/j.lfs.2020.118543

Cited by 30 publications

(29 citation statements)

References 39 publications

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“…The mechanism of decline in ovarian reserve function is complex and related to heredity, immunity, environment, diet, psychological factors, repeated abortion, improper contraceptive methods, and chronic ovarian diseases, among other factors[ 16 - 18 ]. The incidence of decline in ovarian reserve function caused by increases in life and work pressures placed on modern women is increasing every year, with a tendency to occur at younger ages.…”

Section: Discussionmentioning

confidence: 99%

Clinical observation of Kuntai capsule combined with Fenmotong in treatment of decline of ovarian reserve function

Lin

Chen

Wang

et al. 2021

WJCC

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BACKGROUND Decreased ovarian reserve function is an ovarian hypofunction disease that occurs in women before 40 years of age, leading to a decline in fertility and perimenopausal symptoms, such as irregular menstruation, amenorrhea, infertility, decreased libido, and autonomic nervous dysfunction. Fenmatong (FMT) is a compound mixture of estradiol tablets and estradiol didroxyprogesterone tablets, which can improve ovarian reserve function by supplementation of exogenous estrogen. However, this treatment has also been shown to cause breast pain, gastrointestinal discomfort, irregular vaginal bleeding, and changes in sexual desire. In severe cases, FMT can promote the development of breast cancer, endometrial cancer, and venous embolic disease. AIM To observe the effects of Kuntai capsules and FMT on endocrine indexes and uterine artery blood circulation in patients with decreased ovarian reserve function. METHODS Patients (130) with decreased ovarian reserve function, who were treated in our hospital from May 2018 to May 2020, were divided into two groups: The FMT group, in which patients were treated with FMT, and the observation group, in which patients were treated with Kuntai capsules. Chinese medicine symptom scores, uterine artery blood flow parameters, ovarian ultrasound test indexes, pictorial blood loss assessment chart (PBAC) scores, and hormone levels were recorded, and total effective rates were calculated for both groups. RESULTS The total effective rate in the observation group was higher than that in the FMT group ( P < 0.05).After treatment, primary symptoms, including low menstrual volume, delayed menstruation, red color and thick consistency of menses, dizziness, palpitation, weakness at the waist and knee, insomnia and excessive dreaming, irritability, and dryness and astringency of the pudendal canal in the observation group decreased, and scores for primary and secondary symptoms in the observation group were significantly lower than those in the FMT group ( P < 0.05).The systolic peak flow rate (PSV), end-diastolic flow rate (EDV), ovarian diameter, sinus follicle count, and resistance index (RI) of the uterine arteries in the observation group and FMT group increased after treatment. Notably, the PSV, EDV, ovarian diameter, and antral follicle count in the observation group were higher than those in the FMT group, whereas the RI in the observation group was lower than that in the FMT group ( P < 0.05).The PBAC scores in the observation and FMT groups increased after treatment, with that in the observation group becoming significantly higher than that in the FMT group ( P < 0.05). After treatment, estradiol (E2) and anti-Mullerian hormone (AMH) levels increased, whereas follicle-stimulating hormone (FSH) levels decreased in the observation group and FMT group; E2 and AMH levels beca...

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Section: Discussionmentioning

confidence: 99%

Clinical observation of Kuntai capsule combined with Fenmotong in treatment of decline of ovarian reserve function

Lin

Chen

Wang

et al. 2021

WJCC

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“…POI induced by 4-vinylcyclohexene diepoxide (VCD) has been increasingly used in recent years as a model for testing various therapies. In previous research, it was found that long-term, high-dose VCD not only kills small follicles as part of the pathogenesis of premature ovarian failure, but also accelerates the development and discharge of follicles in the growth phase [17] . Combined exposure to VCD and phthalates signi cantly reduced the numbers of primary follicles and consequently increased the risk of premature menopause; combined exposure to phthalates and VCD in early menopausal women is likely to aggravate POI [18] .…”

Section: Introductionmentioning

confidence: 99%

Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Xing

et al. 2022

Preprint

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Background Premature ovarian insufficiency (POI) is a common clinical problem but there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. Methods Female Sprague–Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. Results VCD significantly damaged the rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs could remarkably suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1β and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors. Conclusions Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.

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“…VCD is a novel ovarian toxic substance that induces POF to exhibit unique advantages in dynamic simulation of human ovarian decline in an animal model [ 11 ]. The VCD-induced POF model has a high success rate and the persistent effects [ 12 ]. Apoptosis of oocyte and granulosa cells (GCs) has been identified as one possible underlying mechanism for VCD-induced POF, which leads primordial and primary follicles to be destroyed [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of low intensity pulsed ultrasound on expression of B-cell lymphoma-2 and BCL2-Associated X in premature ovarian failure mice induced by 4-vinylcyclohexene diepoxide

Xia

Qin³

et al. 2021

Reprod Biol Endocrinol

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Background Premature ovarian failure (POF) is a common disease in the field of Gynecology. Low intensity pulsed ultrasound (LIPUS) can promote tissue repair and improve function. This study was performed to determine the effects of LIPUS on granulosa cells (GCs) apoptosis and protein expression of B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) in 4-vinylcyclohexene diepoxide (VCD)-induced POF mice and investigate the mechanisms of LIPUS on ovarian function and reserve capacity. Methods The current POF mice model was administrated with VCD (160 mg/kg) by intraperitoneal injection for 15 consecutive days. The mice were divided into the POF group, LIPUS group and control group. In the LIPUS group, the right ovary of mice was treated by LIPUS (acoustic intensity was 200 mW/cm2, frequency was 0.3 MHz, and duty cycle was 20%) for 20 min, 15 consecutive days from day 16. The mice of the POF group and control group were treated without ultrasonic output. The basic observation and body weight were recorded. Hematoxylin and eosin staining (H&E staining) and enzyme-linked immunosorbent assay (ELISA) were applied to detect ovarian follicle development, ovarian morphology and sex hormone secretion. Ovarian GCs apoptosis was detected by TUNEL assay and immunohistochemistry. Results The results showed that VCD can induce estrus cycle disorder, follicular atresia, sex hormone secretion decreased and GCs apoptosis in mice to establish POF model successfully. LIPUS significantly promoted follicular development, increased sex hormone secretion, inhibited excessive follicular atresia and GCs apoptosis. The mechanism might be achieved by increasing the protein expression of Bcl-2 and decreasing the expression of Bax in ovaries. Conclusions LIPUS can improve the POF induced by VCD. These findings have the potential to provide novel methodological foundation for the future research, which help treat POF patients in the clinic.

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Systemic changes in a mouse model of VCD-induced premature ovarian failure

Cited by 30 publications

References 39 publications

Clinical observation of Kuntai capsule combined with Fenmotong in treatment of decline of ovarian reserve function

Clinical observation of Kuntai capsule combined with Fenmotong in treatment of decline of ovarian reserve function

Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Effects of low intensity pulsed ultrasound on expression of B-cell lymphoma-2 and BCL2-Associated X in premature ovarian failure mice induced by 4-vinylcyclohexene diepoxide

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