Metformin protects against mouse oocyte apoptosis defects induced by arecoline

Li, Weidong; Zang, Chuan‐jie; Yin, Shen; Shen, Wei; Sun, Qing‐Yuan; Zhao, Minghui

doi:10.1111/cpr.12809

Cited by 29 publications

(20 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, as evidenced by IF and WB analyses, L-MET rearranged the disordered cytoskeleton of HTMC. This finding was supported by a study conducted by Li et al ( Li, et al,2020 ), who showed that 50 μM metformin protected oocytes against cytoskeleton destruction. Interestingly, the time course of structural changes in the TM was consistent with the observed pharmacodynamics of metformin on IOP, significantly decreasing 2 and 3 weeks of OHT because of MET treatment, which was consistent with the known effects of other ROCK regulators ( Lin, et al,2018 ; McMurtry, et al,2010 ).…”

Section: Discussionsupporting

confidence: 70%

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

Zhang

Yin

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: This study aimed to investigate the protective effect of metformin on the trabecular meshwork (TM) and explore its molecular mechanisms in vivo and in vitro. Methods: Ocular hypertension (OHT) mouse models were induced with dexamethasone (DEX) and further treated with metformin to determine its IOP lowering effect. Cultured human TM cells (HTMC) were pre-stimulated with tert-butyl hydroperoxide (tBHP) to induce oxidative damage and then supplemented with metformin for another 24 h. The expression of fibrotic markers and integrin/ROCK signals, including α-SMA, TGF-β, fibronectin, F-actin, integrin beta 1, Rho-associated kinase (ROCK)1/2, AMP-activated protein kinase (AMPK), myosin light chain 1 (MLC 1), and F-actin were determined by western blotting (WB) and immunofluorescence (IF). Reactive oxygen species (ROS) content was analysed using flow cytometry (FCM). Results: Administration of metformin reduced the elevated IOP and alleviated the fibrotic activity of aqueous humour outflow in OHT models. Additionally, metformin rearranged the disordered cytoskeleton in the TM both in vivo and in vitro. Furthermore, metformin significantly inhibited ROS production and activated integrin/ROCK signalling induced by tBHP in HTMC. Conclusion: Metformin reduced the elevated IOP in steroid-induced OHT mouse models and exerted its protective effects against oxidative injury by regulating cytoskeleton remodelling through the integrin/ROCK pathway. This study provides new insights into metformin use and preclinical evidence for the potential treatment of primary open-angle glaucoma. Funding: This work was supported by the Key R&D Program of Zhejiang (2022C03112), Leading Scientific and Technological Innovation Talents in Zhejiang Province (2021R52012), National Key R&D Program of China (2020YFC2008200), Zhejiang Provincial National Science Foundation of China (LQ18H120010), Key Innovation and Guidance Program of the Eye Hospital, School of Ophthalmology & Optometry,Wenzhou Medical University (YNZD 2201903), and the Wenzhou Municipal Technological Innovation Program of High-level Talents (No. 604090352/577).

show abstract

Section: Discussionsupporting

confidence: 70%

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

Zhang

Yin

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Next, we discussed the possible reasons for the reduced maturation and reprogramming ability of bovine oocytes after calcium ion reduction. Mitochondrial dysfunction can induce excessive ROS production, resulting in oxidative stress and damage to cells ( Li et al, 2020 ). Therefore, we detected ROS levels in the low-calcium model, and the results showed that low calcium led to the excessive production of ROS ( Figures 4A,B ), and SOD2, as the most important antioxidant enzyme to remove ROS in cells, mRNA expression level was significantly reduced ( Figure 4C ), and oxidative stress was induced.…”

Section: Discussionmentioning

confidence: 99%

The Role of Ca2 + in Maturation and Reprogramming of Bovine Oocytes: A System Study of Low-Calcium Model

Meng

Hao

Liu

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

[Ca2+]i is essential for mammalian oocyte maturation and early embryonic development, as those processes are Ca2+ dependent. In the present study, we investigated the effect of [Ca2+]i on in vitro maturation and reprogramming of oocytes in a lower calcium model of oocyte at metaphase II (MII) stage, which was established by adding cell-permeant Ca2+ chelator BAPTA-AM to the maturation medium. Results showed that the extrusion of the first polar body (PB1) was delayed, and oocyte cytoplasmic maturation, including mitochondrial and endoplasmic reticulum distribution, was impaired in lower calcium model. The low-calcium-model oocytes presented a poor developmental phenotype of somatic cell nuclear transfer (SCNT) embryos at the beginning of activation of zygotic genome. At the same time, oxidative stress and apoptosis were observed in the low-calcium-model oocytes; subsequently, an RNA-seq analysis of the lower-calcium-model oocytes screened 24 genes responsible for the poor oocyte reprogramming, and six genes (ID1, SOX2, DPPA3, ASF1A, MSL3, and KDM6B) were identified by quantitative PCR. Analyzing the expression of these genes is helpful to elucidate the mechanisms of [Ca2+]i regulating oocyte reprogramming. The most significant difference gene in this enriched item was ID1. Our results showed that the low calcium might give rise to oxidative stress and apoptosis, resulting in impaired maturation of bovine oocytes and possibly affecting subsequent reprogramming ability through the reduction of ID1.

show abstract

“…Female mice were subjected to superovulation and oocytes were collected as previously described ( Li et al, 2019 ; Li et al, 2020 ). Briefly, 4–6 week-old ICR female mice were intraperitoneally injected with 10 IU pregnant mare serum gonadotropin (PMSG, NSHF, China) diluted in normal saline.…”

Section: Methodsmentioning

confidence: 99%

Aristolochic acid I exposure decreases oocyte quality

Zhang

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Oocyte quality is a determinant of a successful pregnancy. The final step of oocyte development is oocyte maturation, which is susceptible to environmental exposures. Aristolochic acids (AAs), widely existing in Aristolochia and Asarum plants that have been used in traditional medicine, can result in a smaller ovary and fewer superovulated oocytes after in vivo exposure to mice. However, whether AAs affect oocyte maturation and the underlying mechanism(s) are unclear. In this study, we focused on the effect of Aristolochic acid I (AAI), a major compound of AAs, on the maturation of in vitro cultured mouse oocytes. We showed that AAI exposure significantly decreased oocyte quality, including elevated aneuploidy, accompanied by aberrant chiasma patterns and spindle organization, and decreased first polar body extrusion and fertilization capability. Moreover, embryo development potential was also dramatically decreased. Further analyses revealed that AAI exposure significantly decreased mitochondrial membrane potential and ATP synthesis and increased the level of reactive oxygen species (ROS), implying impaired mitochondrial function. Insufficient ATP supply can cause aberrant spindle assembly and excessive ROS can cause premature loss of sister chromatid cohesion and thus alterations in chiasma patterns. Both aberrant spindles and changed chiasma patterns can contribute to chromosome misalignment and thus aneuploidy. Therefore, AAI exposure decreases oocyte quality probably via impairing mitochondrial function.

show abstract

Metformin protects against mouse oocyte apoptosis defects induced by arecoline

Cited by 29 publications

References 75 publications

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

The Role of Ca2 + in Maturation and Reprogramming of Bovine Oocytes: A System Study of Low-Calcium Model

Aristolochic acid I exposure decreases oocyte quality

Contact Info

Product

Resources

About