Comparison of Animal Models for Premature Ovarian Insufficiency Induced by Different Doses of Cyclophosphamide: a Network Meta‑analysis

Qi, Yiwen; Zhu, Yuemeng; Li, Bin

doi:10.21203/rs.3.rs-1243777/v1

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…Z., 2013 ; Nie, X et al, 2018 ). Clinical studies showed that patients in the POF group were found to have significantly higher FSH and LH serum concentrations and lower E 2 serum levels when compared to healthy controls ( Podfigurna, A et al, 2018 ; Qi et al, 2022 ). Our hormone level results are consistent with our previous findings ( Kuang et al, 2014 ; Li et al, 2014 ).…”

Section: Discussionmentioning

confidence: 98%

MiRNA-190a-5p promotes primordial follicle hyperactivation by targeting PHLPP1 in premature ovarian failure

Zhang

Han

et al. 2022

Front. Genet.

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We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p, miRNA-27b-3p, miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD rats were injected with VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E2) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of target miRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways.

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Section: Discussionmentioning

confidence: 98%

MiRNA-190a-5p promotes primordial follicle hyperactivation by targeting PHLPP1 in premature ovarian failure

Zhang

Han

et al. 2022

Front. Genet.

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“…A previous study has reported that for the construction of POI mouse models, cyclophosphamide (CTX) (120 mg/kg)/busulfan (12 mg/kg) treatment for at least 2 weeks or cisplatin (2 mg/kg) treatment for more than 10 days was found to be the most effective way to construct POI mice ( 94 ). For the induction of POI rats, a loading dose of 200 mg/kg CTX and a maintenance dose of 8 mg/kg CTX for 14 days is the most effective method ( 95 ). A study has shown that exosomes derived from bone marrow mesenchymal cells (BMSCs) can carry miR-144-5p that can mediate the activation of pI3K/AKT pathway and target ovarian granulosa cells (GCs) damaged by CTX, so as to inhibit GC apoptosis in rats with POI caused by CTX and improve ovarian function ( 96 ).…”

Section: Exosomes and Non-ovarian Cancer Diseasementioning

confidence: 99%

Research progress of extracellular vesicles in the treatment of ovarian diseases (Review)

Zhang,

Zhao,

Han

et al. 2023

Exp Ther Med

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The ovary is an essential reproductive organ in the female organism and its development seriously affects the physical and mental health of female patients. Ovarian diseases include ovarian cancer, premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Women should pay attention to the most effective treatments for this condition because it is one of the most prevalent gynecological illnesses at present. Extracellular vesicles (EVs), which are smaller vesicles that mediate the exchange of cellular information, include the three categories of exosomes, microvesicles and apoptotic bodies. They are able to transport proteins, RNA and other substances to adjacent or distal cells, thus allowing cellular and tissue homeostasis to be maintained. Numerous previous studies have revealed that EVs are crucial for the treatment of ovarian diseases. They are known to transport its contents to ovarian cancer cells as well as other ovarian cells such as granulosa cells, affecting the development of ovarian disease processes. Therefore, this extracellular vesicle may be involved as a target in the therapeutic process of ovarian disease and may have great potential in the treatment of ovarian disease. In the present review, the role of EVs in the development of three ovarian diseases, including ovarian cancer, POI and PCOS, was mainly summarizes. It is expected that this will provide some theoretical support for the treatment of ovarian disease.

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Comparison of Animal Models for Premature Ovarian Insufficiency Induced by Different Doses of Cyclophosphamide: a Network Meta‑analysis

Cited by 2 publications

References 22 publications

MiRNA-190a-5p promotes primordial follicle hyperactivation by targeting PHLPP1 in premature ovarian failure

MiRNA-190a-5p promotes primordial follicle hyperactivation by targeting PHLPP1 in premature ovarian failure

Research progress of extracellular vesicles in the treatment of ovarian diseases (Review)

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