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Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation

Objective: To establish an oxidative stress-induced model of premature ovarian insufficiency (POI) and to explore the effect of SIRT1 and mitochondrial oxidative phosphorylation on the ovarian reserve. Methods: Mice were treated with intraperitoneal injections of 3-nitropropionic acid (3-NPA) at dif...

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Autores principales: Guo, Lu, Liu, Xiaocheng, Chen, Hua, Wang, Weigui, Gu, Chao, Li, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954953/
https://www.ncbi.nlm.nih.gov/pubmed/35275845
http://dx.doi.org/10.18632/aging.203942
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author Guo, Lu
Liu, Xiaocheng
Chen, Hua
Wang, Weigui
Gu, Chao
Li, Bin
author_facet Guo, Lu
Liu, Xiaocheng
Chen, Hua
Wang, Weigui
Gu, Chao
Li, Bin
author_sort Guo, Lu
collection PubMed
description Objective: To establish an oxidative stress-induced model of premature ovarian insufficiency (POI) and to explore the effect of SIRT1 and mitochondrial oxidative phosphorylation on the ovarian reserve. Methods: Mice were treated with intraperitoneal injections of 3-nitropropionic acid (3-NPA) at different doses and for different time periods to induce a model of POI. Subsequently, the efficiency of each regimen was evaluated. The expression of SIRT1 in ovarian tissue was examined. Then, SIRT1 was knocked down in human luteinized granulosa cells (GCs), and its function and related receptor and gene expression were examined. Finally, a SIRT1 antagonist and agonist were used to explore the effects of SIRT1 on ovarian function in vivo and on the change in mitochondrial oxidative phosphorylation complexes (OXPHOS). Results: Decreases in ovarian reserve were successfully induced through the intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks, and SIRT1 was down-regulated in the model group. The knockdown of SIRT1 impaired the estrogen synthesis capacity of human GCs and decreased the expression of related genes. 3-NPA and SIRT1 antagonist Ex-527 decreased ovarian function and inhibited OXPHOS. In contrast, the SIRT1 agonist resveratrol promoted the recovery of ovarian function in the model group and improved OXPHOS. Additionally, P53, CASPASE 3, and BAX were down-regulated and BCL2 was up-regulated in the 3-NPA and Ex-527 groups; opposite trends were observed after resveratrol treatment. Conclusions: The intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks could effectively induce POI. The increase in oxidative stress inhibited SRIT1 and mitochondrial oxidative phosphorylation, inducing follicular apoptosis.
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spelling pubmed-89549532022-03-28 Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation Guo, Lu Liu, Xiaocheng Chen, Hua Wang, Weigui Gu, Chao Li, Bin Aging (Albany NY) Research Paper Objective: To establish an oxidative stress-induced model of premature ovarian insufficiency (POI) and to explore the effect of SIRT1 and mitochondrial oxidative phosphorylation on the ovarian reserve. Methods: Mice were treated with intraperitoneal injections of 3-nitropropionic acid (3-NPA) at different doses and for different time periods to induce a model of POI. Subsequently, the efficiency of each regimen was evaluated. The expression of SIRT1 in ovarian tissue was examined. Then, SIRT1 was knocked down in human luteinized granulosa cells (GCs), and its function and related receptor and gene expression were examined. Finally, a SIRT1 antagonist and agonist were used to explore the effects of SIRT1 on ovarian function in vivo and on the change in mitochondrial oxidative phosphorylation complexes (OXPHOS). Results: Decreases in ovarian reserve were successfully induced through the intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks, and SIRT1 was down-regulated in the model group. The knockdown of SIRT1 impaired the estrogen synthesis capacity of human GCs and decreased the expression of related genes. 3-NPA and SIRT1 antagonist Ex-527 decreased ovarian function and inhibited OXPHOS. In contrast, the SIRT1 agonist resveratrol promoted the recovery of ovarian function in the model group and improved OXPHOS. Additionally, P53, CASPASE 3, and BAX were down-regulated and BCL2 was up-regulated in the 3-NPA and Ex-527 groups; opposite trends were observed after resveratrol treatment. Conclusions: The intraperitoneal injection of 40 mg/kg 3-NPA for 3 weeks could effectively induce POI. The increase in oxidative stress inhibited SRIT1 and mitochondrial oxidative phosphorylation, inducing follicular apoptosis. Impact Journals 2022-03-11 /pmc/articles/PMC8954953/ /pubmed/35275845 http://dx.doi.org/10.18632/aging.203942 Text en Copyright: © 2022 Guo et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Guo, Lu
Liu, Xiaocheng
Chen, Hua
Wang, Weigui
Gu, Chao
Li, Bin
Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title_full Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title_fullStr Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title_full_unstemmed Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title_short Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation
title_sort decrease in ovarian reserve through the inhibition of sirt1-mediated oxidative phosphorylation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954953/
https://www.ncbi.nlm.nih.gov/pubmed/35275845
http://dx.doi.org/10.18632/aging.203942
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