scholarly journals Study on the Reparative Effect of PEGylated Growth Hormone on Ovarian Parameters and Mitochondrial Function of Oocytes From Rats With Premature Ovarian Insufficiency

2021 ◽  
Vol 9 ◽  
Author(s):  
Penghui Feng ◽  
Qiu Xie ◽  
Zhe Liu ◽  
Zaixin Guo ◽  
Ruiyi Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Single Cell ◽  
Estrous Cycle ◽  
Sex Hormones ◽  
Mitochondrial Function ◽  
Ovarian Function ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
And Oxidative Stress

Premature ovarian insufficiency (POI) is a heterogeneous disorder and lacks effective interventions in clinical applications. This research aimed to elucidate the potential effects of recombinant human PEGylated growth hormone (rhGH) on follicular development and mitochondrial function in oocytes as well as ovarian parameters in POI rats induced by the chemotherapeutic agent. The impacts of rhGH on ovarian function before superovulation on follicles, estrous cycle, and sex hormones were evaluated. Oocytes were retrieved to determine oocyte quality and oxidative stress parameters. Single-cell sequencing was applied to investigate the latent regulatory network. This study provides new evidence that a high dosage of rhGH increased the number of retrieved oocytes even though it did not completely restore the disturbed estrous cycle and sex hormones. rhGH attenuated the apoptosis of granulosa cells and oxidative stress response caused by reactive oxygen species (ROS) and mitochondrial superoxide. Additionally, rhGH modulated the energy metabolism of oocytes concerning the mitochondrial membrane potential and ATP content but not mtDNA copy numbers. Based on single-cell transcriptomic analysis, we found that rhGH directly or indirectly promoted the balance of oxidative stress and cellular oxidant detoxification. Four hub genes, Pxmp4, Ehbp1, Mt-cyb, and Enpp6, were identified to be closely related to the repair process in oocytes as potential targets for POI treatment.

scholarly journals Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

2020 ◽  
Author(s):  
huihui zhao ◽  
Wenqing Gu ◽  
Huogui Ouyang ◽  
Wenbin Pan ◽  
Hanbin Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sex Hormones ◽  
Ovarian Function ◽  
Target Prediction ◽  
Absolute Quantification ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Real Time Quantitative Pcr ◽  
Quantification Analysis

Abstract Background Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents a major cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear. Methods The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA). Results We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p , which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p . Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P <0.01; E 2 : P <0.01; FSH: P <0.01). Conclusions Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes aggravated POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

scholarly journals Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

2020 ◽  
Author(s):  
huihui zhao ◽  
Wenqing Gu ◽  
Huogui Ouyang ◽  
Wenbin Pan ◽  
Hanbin Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sex Hormones ◽  
Ovarian Function ◽  
Target Prediction ◽  
Absolute Quantification ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Real Time Quantitative Pcr ◽  
Quantification Analysis

Abstract Background: Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents an existing challenge cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear.Methods: The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA).Results: We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p, which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p. Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P < 0.01; E2: P < 0.01; FSH: P < 0.01).Conclusions: Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes could aggravate POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

scholarly journals Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4

2020 ◽  
Author(s):  
huihui zhao ◽  
Wenqing Gu ◽  
Huogui Ouyang ◽  
Wenbin Pan ◽  
Hanbin Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sex Hormones ◽  
Ovarian Function ◽  
Target Prediction ◽  
Absolute Quantification ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Real Time Quantitative Pcr ◽  
Quantification Analysis

Abstract Background: Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents an existing challenge cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear.Methods: The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA).Results: We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p, which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p. Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P < 0.01; E2: P < 0.01; FSH: P < 0.01).Conclusions: Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes could aggravate POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.

scholarly journals Hyperbaric Oxygen Treatment: Effects on Mitochondrial Function and Oxidative Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1827
Author(s):  
Nofar Schottlender ◽  
Irit Gottfried ◽  
Uri Ashery
Keyword(s):  
Oxidative Stress ◽  
Hyperbaric Oxygen ◽  
Mitochondrial Function ◽  
Defense Mechanisms ◽  
Term Treatment ◽  
Mitochondrial Activity ◽  
Hyperbaric Oxygen Treatment ◽  
Oxygen Treatment ◽  
Long Term Treatment ◽  
And Oxidative Stress

Hyperbaric oxygen treatment (HBOT)—the administration of 100% oxygen at atmospheric pressure (ATA) greater than 1 ATA—increases the proportion of dissolved oxygen in the blood five- to twenty-fold. This increase in accessible oxygen places the mitochondrion—the organelle that consumes most of the oxygen that we breathe—at the epicenter of HBOT’s effects. As the mitochondrion is also a major site for the production of reactive oxygen species (ROS), it is possible that HBOT will increase also oxidative stress. Depending on the conditions of the HBO treatment (duration, pressure, umber of treatments), short-term treatments have been shown to have deleterious effects on both mitochondrial activity and production of ROS. Long-term treatment, on the other hand, improves mitochondrial activity and leads to a decrease in ROS levels, partially due to the effects of HBOT, which increases antioxidant defense mechanisms. Many diseases and conditions are characterized by mitochondrial dysfunction and imbalance between ROS and antioxidant scavengers, suggesting potential therapeutic intervention for HBOT. In the present review, we will present current views on the effects of HBOT on mitochondrial function and oxidative stress, the interplay between them and the implications for several diseases.

scholarly journals Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Aβ-Exposed Hippocampal Neurons

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Nora E. Gray ◽  
Jonathan A. Zweig ◽  
Donald G. Matthews ◽  
Maya Caruso ◽  
Joseph F. Quinn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Neuroblastoma Cells ◽  
Water Extract ◽  
Centella Asiatica ◽  
Antioxidant Response ◽  
And Oxidative Stress

Centella asiatica has been used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) protects against the deleterious effects of amyloid-β (Aβ) in neuroblastoma cells and attenuates Aβ-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals. This study investigates the effects of CAW on neuronal metabolism and oxidative stress in isolated Aβ-expressing neurons. Hippocampal neurons from amyloid precursor protein overexpressing Tg2576 mice and wild-type (WT) littermates were treated with CAW. In both genotypes, CAW increased the expression of antioxidant response genes which attenuated the Aβ-induced elevations in reactive oxygen species (ROS) and lipid peroxidation in Tg2576 neurons. CAW also improved mitochondrial function in both genotypes and increased the expression of electron transport chain enzymes and mitochondrial labeling, suggesting an increase in mitochondrial content. These data show that CAW protects against mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons which could contribute to the beneficial effects of the extract observed in vivo. Since CAW also improved mitochondrial function in the absence of Aβ, these results suggest a broader utility for other conditions where neuronal mitochondrial dysfunction occurs.

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