Protective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovaries

Zhang, Jinjin; Li, Fang; Shi, Lijun; Lai, Zhiwen; Lu, Zhongxin; Xiong, Jiaqiang; Wu, Meng; Luo, Aiyue; Wang, Shixuan

doi:10.1016/j.jep.2016.11.014

Cited by 31 publications

(18 citation statements)

References 53 publications

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“…In this accelerated ovarian aging model, the number of primordial follicles was substantially decreased, whereas the number of atretic follicles was significantly increased. Conversely, the decreased numbers of primordial, primary and secondary follicles resulted in a decreased number of total follicles, consistent with the results of a previous report [3]. In addition to the decrease in the number of antral follicles, the AMH and INH B decline was increased by consecutive superovulation in our study.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, we examined the ovary aging effect of consecutive superovulation on mouse ovaries and generated an ovary aging mouse model by consecutive superovulation. In our study, both the primordial follicle pool and ovarian function were significantly decreased in the model mice, consistent with the characteristics of ovarian aging [3]; the model group displayed lower hormone levels and higher ROS and cell apoptosis levels than the control group, indicating that the model group displayed ovarian aging.…”

Section: Discussionsupporting

confidence: 84%

“…This study showed that consecutive superovulation primarily affects the function of ovaries in female mice by decreasing E2 and P and increasing FSH and LH. Many reports have shown that repeated superovulation directly induces oxidative stress in vivo , attenuates FSH bioactivity and inhibits E2 production in granulosa cells [3, 28]. These results demonstrated that consecutive superovulation may affect ovarian endocrine function, and the trend was consistent with that in NOA mice.…”

Section: Discussionsupporting

confidence: 78%

“…The estrous cycle of female mice is similar to that of humans, although the estrous cycle of mice is shorter than that of humans [3]. Currently, mouse models of female reproductive aging are divided into two categories: genetic mutation animal models, such as the follitropin receptor knockout animal model [4, 5] and the dioxin/aryl hydrocarbon receptor knockout animal model [6, 7]; and poison damage models, such as the 4-vinylcyclohexene diepoxide-induced female reproductive aging model [8, 9] and the D-galactose-induced female reproductive aging model [10-12].…”

Section: Introductionmentioning

confidence: 99%

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Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

Nie

Dai

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

Nie

Dai

Zheng

et al. 2018

Cell Physiol Biochem

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“…Therefore, elucidation of the mechanism for POF development is critical for the clinical treatment of POF disease[ 54 ]. The estrous cycle of female mice is similar to that of humans, although the estrous cycle of mice is shorter than that of humans[ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

Bahrehbar¹,

Valojerdi²,

Esfandiari³

et al. 2020

WJSC

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BACKGROUND Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. According to previous reports, various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Human embryonic stem cells (ES) provide an alternative source for mesenchymal stem cells (MSCs) because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics. Embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs. However, possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated. AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells (BM-MSCs) in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure. METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF. Either human ES-MSCs or BM-MSCs were transplanted into these mice. Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ES-MSCs and/or BM-MSCs, we evaluated body weight, estrous cyclicity, follicle-stimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation. Moreover, terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling, real-time PCR, Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation. Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor, insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function. RESULTS The human ES-MSCs significantly restored hormone secretion, survival rate and reproductive function in POF mice, which was similar to the results obtained with BM-MSCs. Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles. Notably, the transplanted mice generated new offspring. The results of different analyses showed increases in antiapoptotic and trophic proteins and genes. CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility. The possible mechanisms of human ES-MSC were related to promotion of follicular dev...

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Effects of Environment and Lifestyle Factors on Premature Ovarian Failure

Yang

Huang

Yuan

2021

Environment and Female Reproductive Health

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Protective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovaries

Cited by 31 publications

References 53 publications

Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

Effects of Environment and Lifestyle Factors on Premature Ovarian Failure

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