Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis

Ragonese, Francesco; Monarca, Lorenzo; Luca, Antonella De; Mancinelli, Loretta; Mariani, Monica; Corbucci, Cristina; Gerli, Sandro; Iannitti, Rossana Giulietta; Leonardi, Lucio; Fioretti, Bernard

doi:10.1016/j.fertnstert.2020.08.016

Cited by 34 publications

(25 citation statements)

References 48 publications

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“…Although we did not observe significant ATP production at low doses of RES on primary GC, it indicates the potential benefits that this compound may exert on cell viability. Our findings are supported by Ragonese et al, who reported ATP increase after the addition of low doses of RES (3 μM) on human GC [41]. Li et al showed that 10 μM of RES increased ATP levels in human GC compared with the control group, after 24 h of treatment [42].…”

Section: Discussionsupporting

confidence: 89%

Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

et al. 2021

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Resveratrol is a phytoalexin present in plant-derived foods, including grape’s skin, cocoa, and peanuts. Evidence suggests that it has beneficial effects on human health because of its antioxidant properties. However, there is limited knowledge about the part played by resveratrol in ovarian function. In this paper, the influence of resveratrol on granulosa cells (GC) was evaluated. In addition to being the main estradiol producers, GC are in direct contact with the oocyte, playing a fundamental role in its growth and development. The cell line COV434 and human granulosa cells (hGC), obtained from women undergoing assisted reproductive technology (ART), were used. GC were treated with resveratrol (0.001–20 μM) at different times (24–72 h). Low concentrations of this compound suggest a protective role, as they tend to reduce ROS/RNS formation after inducement of stress. On the contrary, high concentrations of resveratrol affect GC viability and steroidogenic function. As it may act as a direct modulator of GC oxidative balance, this work may help to clarify the impact of resveratrol on GC and the usefulness of this antioxidant as adjunct to infertility treatments.

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Section: Discussionsupporting

confidence: 89%

Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

et al. 2021

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“…Mitochondrial ATP generation is critically valuable in oocytes and early mammalian embryos (33).Meanwhile, MMP is a biomarker of mitochondrial activity that is vital in ATP synthesis, redox balance, signaling, and metabolism (34,35). Recent studies have found that lower MMP and ATP levels are closely related to decreased mitochondrial function in GCs (36).…”

Section: Discussionmentioning

confidence: 99%

Investigation of He’s Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function

Miao

Zhao²,

Chen³

et al. 2023

Front. Endocrinol.

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BackgroundPrimary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and low estrogen symptoms. Traditional Chinese medicine is regarded as an effective treatment for POI. However, the therapeutic mechanism of it is unclear.MethodsIn this study, a mouse model of primary ovarian insufficiency was established by intraperitoneal injection of cyclophosphamide (CTX) and He’s Yang Chao Recipe (HSYC) concentrate was used for intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone and Follicle Stimulating Hormone) and Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Pathological changes in ovarian tissue were evaluated by hematoxylin and eosin staining, and flow cytometry was used to determine reactive oxygen species content and mitochondrial membrane potential levels in granulosa cells. Mitochondrial distribution and morphology were investigated using immunofluorescence staining. The level of mitophagy was evaluated by LC3 immunofluorescence staining and autophagosome counts using electron microscopy. Western blotting and qPCR were used to detect the expression of proteins and genes related to mitophagy and the NLRP3 inflammasome.ResultsAfter HSYC treatment, the ovarian damage was milder than in the CTX group. Compared with the CTX group; SOD, GSH-Px, and the total antioxidant capacity were significantly increased, while MDA and ROS were decreased in the HSYC treatment groups. Furthermore, mitochondrial distribution and membrane potential levels were improved after HSYC treatment compared to the CTX group. After the HSYC treatment, the LC3 fluorescent intensity and autophagosome counts were decreased. Similarly, mitophagy related markers PINK1, Parkin, LC3, and Beclin1 were decreased, while p62 was significantly increased, compared with the CTX groups. The mRNA and protein expression of NLRP3 inflammasome, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β were significantly decreased in the HSYC treatment groups.ConclusionThis is the first study in molecular mechanisms underlying HSYC against granulosa cell injury in POI. HSYC protects ovaries from CTX-induced ovarian damage and oxidative stress. HSYC enhanced ovarian function in mice with primary ovarian insufficiency by inhibiting PINK1-Parkin mitophagy and NLRP3 inflammasome activation.

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“…The first step of steroid biosynthesis occurs in mitochondria, and it is closely associated with ATP production and mtDNA copy numbers of mitochondria (Atif et al, 2021; Chien et al, 2017). Ragonese et al (2021) reported that in human, mitochondria ATP produced by oxidative phosphorylation is important to induce granulosa cells proliferation and differentiation. Our results showed that P4 biosynthesis and proliferation of granulosa cells both increased significantly after follicle selection.…”

Section: Discussionmentioning

confidence: 99%

MFN2 regulates progesterone biosynthesis and proliferation of granulosa cells during follicle selection in hens

Hou,

Hu,

et al. 2023

Journal Cellular Physiology

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Follicle selection in hens refers to a biological process that only one small yellow follicle (SYF) is selected daily or near‐daily for following hierarchical development (from F5/F6 to F1) until ovulation. MFN2 is a kind of GTPases located on the mitochondrial outer membrane, which plays a crucial role in mitochondrial fusion. This study aimed to elucidate the role of MFN2 in proliferation and progesterone biosynthesis of granulosa cells (GCs) during follicle selection in hens. The results showed that GCs began to produce progesterone (P4) after follicle selection, accompanied with changes from multi‐layer with flat cells to single layer with cubic cells. MFN2 was detected in GCs of follicles from SYF to F1. After follicle selection, the expression level of MFN2 in GCs upregulated significantly, accompanied with increases in P4 biosynthesis, ATP production, mitochondrial DNA (mtDNA) copy numbers of granulosa cells. FSH (80 ng/mL) facilitated the effects of P4 biosynthesis and secretion, ATP production, mtDNA copy numbers, cell proliferation and the MFN2 transcription of granulosa cells from F5 (F5G) in vitro. However, FSH treatment did not promote P4 secretion in granulosa cells from SYF (SYFG) in vitro. Meanwhile, we observed that change fold of MFN2 transcription, ATP production, mtDNA copy numbers and cell proliferation rate in F5G after treatment with FSH were greater than those in SYFG. Furthermore, expression levels of MFN2 protein and messenger RNA in F5G were significantly higher than those in SYFG after treatment with FSH. P4 biosynthesis, ATP production, mtDNA copy numbers as well as cell proliferation reduced significantly in F5G with MFN2 knockdown. Oppositely, P4 biosynthesis, ATP production, mtDNA copy numbers and cell proliferation increased significantly in SYFG after the overexpression of MFN2. Our results suggest that the upregulation of MFN2 may be involved in the initiation of P4 biosynthesis, and promotion of GCs proliferation during follicle selection.

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Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis

Cited by 34 publications

References 48 publications

Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

Investigation of He’s Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function

MFN2 regulates progesterone biosynthesis and proliferation of granulosa cells during follicle selection in hens

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