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A peer-reviewed article of this preprint also exists.
This version is not peer-reviewed
Submitted:
25 July 2023
Posted:
26 July 2023
Read the latest preprint version here
Mitochondrial Function | Effect of PCOS Condition on Mitochondrial Function | Model - Species | PCOS Model/Diagnosis | Treatment timeframe | Method | Therapeutic Intervention | Reference |
---|---|---|---|---|---|---|---|
Biogenesis | Decreased PGC1 |
Rat | IP Letrozole + HFD | 21 days, 21 days, 35 days, 12 weeks | qPCR, WB | Cangfudaotan (IG) and metformin (IG) increased PGC1 to control levels | [1] |
Rat | IG Letrozole | 21 days | WB | [2] | |||
Mouse | SQ DHT | 35 days | WB | Overexpressing SIRT3 in vivo increased PGC1 back to control levels | |||
Mouse | HF/HGD (58% kcal fat + sucrose) | 12 weeks | qPCR | Neurokinin-B antagonist increased PGC1 back to control levels | [3] | ||
Decreased TFAM | Mouse | SQ DHEA | 20 days | WB | 1) L-carnitine (LC) + acetyl-L-carnitine (ACL) 2) LC and ACL plus propionyl-L-carnitine Both formulations increased TFAM compared to DHEA alone and controls |
[4] | |
Rat | IG Letrozole | 21 days | WB | [2] | |||
Mouse | HF/HGD (58% kcal fat + sucrose) | 12 weeks | qPCR | Neurokinin-B antagonist increased TFAM back to control levels | [3] | ||
Decreased NRF1 | Mouse | HF/HGD (58% kcal fat + sucrose) | 12 weeks | qPCR | Neurokinin-B antagonist increased NRF1 back to control levels | [3] | |
Mitochondrial Genome | Increased mtDNA fragmentation | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | qPCR | Cangfudaotan (IG) and metformin (IG) decreased mtDNA damage and fragmentation | [1] |
Ultrastructure | Membrane swelling & ruptures | Rat | IP Letrozole + HFD | 21 days | EM | % of total damaged mitochondria decreased with both metformin (IG) or cangfudaotan (IG) but were still higher than control levels | [1] |
Metabolism | Increased basal, maximal and ATP-linked OCR, proton leak | Mice - offspring | DHT injection in dams post coitus, assessed pup neonatal ovaries | GD 16.5, 17.5, 18.5 | XF (Agilent) of whole neonatal ovaries | [5] | |
Decreased OCR, RCR | Rat | IP letrozole + HFD | 21 days | Oxytherm Clark-type electrode on isolated mitochondria | Cangfudaotan (IG) increased OCR, RCR | [1] | |
Decreased ATP | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | Colorimetric ATP assay | SeNP alone and in combination with metformin increased ATP (most increase in combination) | [6] | |
Rat | IP letrozole + HFD | 21 days | ATP assay | Cangfudaotan (IG) increased ATP levels | [1] | ||
No difference in ATP | Mice - offspring | DHT injection in dams post coitus, assessed pup neonatal ovaries | GD 16.5, 17.5, 18.5 | XF (Agilent) of whole neonatal ovaries | [5] | ||
Decreased activity of mitochondrial complex enzymes | Rat | IP letrozole + HFD | 21 days | Complex enzymes activity assay | Cangfudaotan (IG) increased mitochondrial complex activity | [1] | |
Decreased Complex I activity | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | Complex I enzyme activity assay | SeNP alone and in combination with metformin increased Complex 1 activity (most increase in combination) | [6] | |
Rat | SQ DHEA | 20 days | Bushen Huatan Granules (OG) increased activity of complex I | [7] | |||
Decreased Complex III, IV activity | SQ DHEA | 20 days | Complex III, IV enzyme activity assays | Bushen Huatan Granules (OG) increased activity of complex III and IV | [7] | ||
Decreased Complex IV (Cox6a2 subunit) | Mice - offspring | DHT injection in dams post coitus, assessed pup neonatal ovaries | GD 16.5, 17.5, 18.5 | RNAseq | [5] | ||
Decreased citrate synthase activity | Rat | Letrozole (OG) | 21 days | Citrate synthase activity assay | Metformin (OG) and sodium selenite (OG) increased mitochondrial citrate synthase activity but was still lower than control group | [8] | |
Decreased MMP | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days |
JC-1 staining | SeNP alone and in combination with metformin increased MMP (most increase in combination) | [6] | |
Rat | IP letrozole + HFD | Cangfudaotan (IG) or metformin (IG) increased MMP | [1] | ||||
Dynamics | Decreased MFN1 | Rat | IP letrozole + HFD | 21 days | qPCR/WB | Cangfudaotan (IG) or metformin (IG) increased MFN1 | [1] |
Rat | IG Letrozole | 21 days | WB | [2] | |||
Decreased MFN2 | Rat | IP letrozole + HFD | 21 days | qPCR/WB | Cangfudaotan (IG) or metformin (IG) increased MFN2 | [1] | |
Rat | Letrozole (OG) | 21 days | qPCR/ELISA kit | Metformin (OG) and sodium selenite (OG) increased MFN2, but still lower than control group | [8] | ||
Rat | IG Letrozole | 21 days | WB | [2] | |||
Decreased OPA1 | Rat | IP letrozole + HFD | 21 days | qPCR/WB | Cangfudaotan (IG) or metformin (IG) increased OPA1 | [1] | |
Increased DRP1 | Rat | IP letrozole + HFD | 21 days | qPCR/WB | Cangfudaotan (IG) or metformin (IG) decreased DRP1 | [1] | |
Rat | Letrozole (OG) | 21 days | qPCR/ELISA kit | Metformin (OG) and sodium selenite (OG) decreased DRP1, but still higher than control group | [8] | ||
Rat | IG Letrozole | 21 days | WB | [2] | |||
Increased FIS1 | Rat | IP letrozole + HFD | 21 days | qPCR/WB | Cangfudaotan (IG) or metformin (IG) decreased FIS1 | [1] | |
Rat | IG Letrozole | 21 days | WB | [2] | |||
ROS & Repair | Increased ROS | Rat | IP letrozole + HFD | 21 days | DCF staining | Cangfudaotan (IG) or metformin (IG) decreased ROS | [1] |
Rat | IG Letrozole | 21 days | Activity to produce superoxide anion assay | [2] | |||
Increased mitochondrial superoxide | Rat | SQ DHEA | 20 days | MitoSOX staining | Bushen Huatan Granules (OG) decreased mitochondrial superoxide | [7] | |
Increased lipid peroxidation | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | MDA assay | SeNP alone or in combination with metformin decreased lipid peroxidation | [6] | |
Rat | Letrozole (OG) | 21 days | Metformin (OG) and sodium selenite (OG) decreased lipid peroxidation, but still higher than control group | [8] | |||
Rat | SQ DHEA | 21 days | [9] | ||||
Rat | IG Letrozole | 21 days | [2] | ||||
Mouse | SQ DHEA | 20 days | Genistein decreased lipid peroxidation | [10] | |||
Increased protein oxidation | Rat | Letrozole (OG) | 21 days | DNPH reaction assay | Metformin (OG) and sodium selenite (OG) decreased protein oxidation, but still higher than control group | [8] | |
Increased DNA oxidation | Mouse | SQ DHEA | 20 days | 8-OHdG ELISA | Genistein decreased DNA oxidation levels | [10] | |
Decreased antioxidant capacity | Rat | Letrozole (OG) | 21 days | Ferric reducing antioxidant power assay | Metformin (OG) and sodium selenite (OG) increased antioxidant capacity, but still lower than control group | [8] | |
Decreased SOD activity | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | SOD enzyme activity assay | SeNP alone or in combination with metformin increased SOD levels | [6] | |
Rat | SQ DHEA | 21 days | [9] | ||||
Mouse | SQ DHEA | 20 days | Genistein increased SOD | [10] | |||
Decreased SOD1 | Mouse | HF/HGD (58% kcal fat + sucrose) | 12 weeks | qPCR | Neurokinin-B antagonist increased SOD1 | [3] | |
Increased SOD2 (MnSOD) | Mouse | SQ DHEA | 20 days | WB | 1) LC + ACL & 2) LC, ACL + propionyl-L-carnitine both decreased SOD2 | [4] | |
Rat | IG Letrozole | 21 days | WB | [2] | |||
Decreased GSH | Rat | On day 22 of HFD (46% fat), OG letrozole | 21 days | GSH level | SeNP alone or in combination with metformin increased GSH levels | [6] | |
Decreased GSH-Px (GPx) | Rat | Letrozole (OG) | 21 days | GPx enzyme activity assay | Metformin (OG) and sodium selenite (OG) increased GPx activity, but still lower than control group | [8] | |
Mouse | SQ DHEA | 20 days | GSH-Px level | Genistein increased GSH-Px | [10] | ||
Increased GSH-Px | Rat | IG Letrozole | 21 days | GSH-Px enzyme activity assay | [2] | ||
Decreased GR | Mouse | SQ DHEA | 20 days | GR enzyme activity assay | [10] | ||
Decreased GSH:GSSG ratio | Mouse | SQ DHEA | 20 days | GSH and GSSG level | Genistein increased GSH:GSSG ratio | [10] | |
Decreased CAT activity | Mouse | SQ DHEA | 20 days | CAT enzyme activity assay | Genistein increased CAT activity | [10] | |
Rat | SQ DHEA | 21 days | [9] | ||||
Mouse | HF/HGD (58% kcal fat + sucrose) | 12 weeks | qPCR | Neurokinin-B antagonist increased CAT expression | [3] | ||
Increased opening of mPTP | Rat | IP letrozole + HFD | 21 days | Mitochondrial Membrane Pore Channel Colorimetric Assay | Canfudaton (IG) or metformin (IG) decreased opening of mPTP | [1] | |
Increased levels of Cytochrome C in cytosol than in mitochondria | Rat | SQ DHEA | 20 days | WB | Bushen Huatan Granules (OG) decreased levels of Cytochrome C in cytosol fraction compared to mitochondrial fraction | [7] |
Mitochondrial Function | Effect of PCOS on Mitochondrial Function | Model - Species | PCOS Model/Diagnosis | Treatment timeframe | Method | Therapeutic Intervention | Reference |
---|---|---|---|---|---|---|---|
Biogenesis | Decreased PGC1 | Cell line KGN | 500mM DHT | 24 hours | WB | Overexpression of SIRT3 (cell transfection) increased PGC1 levels comparable to controls | [11] |
Cell line KGN | Palmitic Acid + DHT | Various | qPCR | si-NK3R increased PGC1 | [3] | ||
Decreased TFAM | Mouse | SQ DHEA | 20 days prior to puberty | qPCR | Vitamin D3 (100mM for 24 hours) increased TFAM | [12] | |
Cell line KGN | Palmitic Acid + DHT | Various | qPCR | si-NK3R increased TFAM | [3] | ||
Decreased NRF1 | Cell line KGN | Palmitic Acid + DHT | Various | qPCR | si-NK3R increased NRF1 | [3] | |
Mitochondrial Genome | Decreased mtDNA copy number |
Mouse | SQ DHT | 20 days prior to puberty | qPCR | Vitamin D3 (100mM for 24 hours) increased mtDNA copy number | [12] |
Rat | SQ DHEA | 20 days | qPCR (mtND1:beta-globin) | [13] | |||
Human | Rotterdam | qPCR (mtND1:beta-actin) | [14] | ||||
Increased mtDNA copy number | Cell line KGN | 500nM DHT | 24 hours | qPCR | Overexpression of SIRT3 decreased mtDNA copy number, but increased back to DHT-exposed levels with PGC1a inhibitor | [11] | |
Ultrastructure | Disorganized cristae, vacuoles, less electron dense | Mouse - offspring | DHT injection post coitus, assessed pup neonatal GCs | GD 16.5, 17.5, 18.5 | TEM | [5] | |
Mitochondrial aggregated distribution, cristae dissolution and fracture, presence of vacuoles (66.66% abnormal mitochondria compared to 0% in controls) | Rat | SQ DHEA | 20 days | TEM | [13] | ||
Mitochondrial swelling and membrane defects | Mouse | SQ DHT | 35 days | TEM | Melatonin reduced mitochondrial swelling and membrane defects | [15] | |
Mitochondrial swelling and membrane defects | Human | Rotterdam | TEM | [15] | |||
Less rod-shaped mitochondria, more circular/constricted mitochondria | Rat | Continuous-release DHT pellet implant | 1 month (83μg/day) | TEM | eCG increased rod-shaped mitochondria & decreased circular/constricted mitochondria | [16] | |
Decreased mitochondria amount | Human | Rotterdam | Nonyl acridine orange (NAC) flow cytometry | [17] | |||
Decreased mitochondrial mass, increased mitochondrial fragmentation, constrained cell expansion | Human | Rotterdam | pLV-mitoDsRed plasmid transfection (tags ATP synthase) and imaging | [17] | |||
Metabolism | Decreased ATP levels | Mouse | 100 μM DHEA | 12 hours | ATP assay | Genistein increased ATP levels but still lower than controls. Additional treatment with NRF2 inhibitor ML385 decreased ATP levels compared to genistein alone, but was still higher than DHEA group | [10] |
Rat | SQ DHEA | 20 days | [13] | ||||
Cell line KGN | 500nM DHT | 24 hours | Overexpression of SIRT3 increased ATP, but addition of PGC1a inhibitor reversed this effect | [11] | |||
Human | Rotterdam | [14] | |||||
Decreased Complex I, III, IV activity | Rat | Testosterone (10-5 M) | 24 hours | Complex I/III/IV activity assay | 6 hour incubation with serum from rats receiving Bushen Huatan Granules treatment led to increased activity of complex I, III, IV | [7] | |
Decreased NDUFB8 (Complex I subunit) and ATP5j (ATP synthase subunit) | Rat | SQ DHEA | 20 days | qPCR/WB | [13] | ||
Decreased MMP | Mouse | SQ DHEA | 20 days | JC-1 flow cytometry | Genistein increased MMP but still lower than controls. Additional treatment with NRF2 inhibitor ML385 had similar MMP to DHEA group | [10] | |
Cell line KGN | 500nM DHT | 24 hours | JC-1 staining | Overexpression of SIRT3 increased MMP, but addition of PGC1a inhibitor reversed this effect | [11] | ||
Cell line KGN | 500nM DHT | 24 hours | Melatonin (1000pM for 24 hrs) increased MMP | [15] | |||
Human | Rotterdam | TMRE flow cytometry | [17] | ||||
Human | Rotterdam | Mitotracker Red flow cytometry |
[17] | ||||
Human | Rotterdam | JC-1 Mitochondrial Membrane Potential Kit | [14] | ||||
Increased VDAC1 | Rat | IG letrozole | 21 days | WB | [2] | ||
Decreased VDAC1 | Human | Rotterdam | qPCR/ICC | [18] | |||
Decreased TSPO | Human | Rotterdam | qPCR/ICC | [18] | |||
Dynamics | Increased DRP1 | Rat | Continuous-release DHT pellet implant | 1 month (83μg/day) | WB | [16] | |
ROS & Repair | Increased ROS | Mouse | 100 μM DHEA | 12 hours | DCFH-DA flow cytometry | Genistein decreased ROS | [10] |
Human | Rotterdam | DCFH-DA | [14] | ||||
Increased mitochondrial superoxide | Cell line KGN | 500nM DHT | 24 hours | MitoSOX staining | Overexpression of SIRT3 decreased mitochondrial superoxide, but addition of PGC1-a inhibitor reversed this outcome | [11] | |
Increased lipid peroxidation | Mouse | SQ DHEA | 20 days | MDA assay | Genistein decreased lipid peroxidation | [10] | |
Increased DNA oxidation | Mouse | SQ DHEA | 20 days | 8-OHdG ELISA | Genistein decreased 8-OhdG levels | [10] | |
Decreased SOD, GSH-Px, GR, GSH:GSSG ratio | Mouse | SQ DHEA | 20 days | SOD, GR enzyme activity assays/GSH-Px, GSH:GSSG content assays | Genistein increased SOD, CAT, GSH-Px, GSH:GSSG ratio | [10] | |
Decreased SOD1 | Cell line KGN | Palmitic Acid + DHT | Various | qPCR | si-NK3R increased SOD1 | [3] | |
Decreased CAT | Mouse | SQ DHEA | 20 days | CAT enzyme activity assay | Genistein increased CAT | [10] | |
Cell line KGN | Palmitic Acid + DHT | Various | qPCR | si-NK3R increased CAT | [3] | ||
Upregulation of UPR-MT (mitochondrial unfolded protein response) proteins | Human | Rotterdam | qPCR | [19] | |||
Increased opening of mPTP | Cell line KGN | 500nM DHT | 24 hours | Mitochondrial permeability transition pore assay | Melatonin (1000pM for 24 hrs) decreased opening of mPTP | [15] |
Mitochondrial Function | Effect of PCOS on Mitochondrial Function | Model - Species | PCOS Model/Diagnosis | Treatment timeframe | Method | Therapeutic Intervention | Reference |
---|---|---|---|---|---|---|---|
Biogenesis | No Reports | ||||||
Mitochondrial Genome | Increased mtDNA copy number | Mouse | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | qPCR (mtCO1:tubulin) | [20] | |
No difference in mtDNA copy number | Mouse – offspring | DHT injection in dam post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | qPCR (mtCO1:tubulin) | [5] | ||
Ultrastructure | Disorganized cristae, vacuoles, less electron dense | Mouse – offspring | DHT injection in dam post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | TEM | [5] | |
Mitochondria with malformed cristae with concentric circles, swollen or loss of cristae | Mouse | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | SEM | [20] | ||
Mitochondria have swollen cristae, no electron dense contents and are vacuolated | Mice – offspring | DHT injection in dams post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | TEM | [21] | ||
Abnormal mitochondria distribution | Human/ Mouse | EVs isolated from PCOS patients with non-hyperandrogenic phenotype were co-cultured with control murine oocytes | Mitochondrial Red Fluorescent Probe | [22] | |||
Metabolism | Increased glucose, pyruvate consumption | Human | Rotterdam | Ultra-microfluorometric assay | [23] | ||
Increased ATP levels | Mice | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | ATP assay | [20] | ||
No difference in ATP levels | Mice – offspring | DHT injection in dams post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | [21] | |||
Decreased mitochondrial complex I genes (ND1,ND2,ND5) | Mice | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | qPCR | [20] | ||
Increased mitochondrial complex I and IV genes (ND1, ND6 & CO1, CO2, CO3) | Mice – offspring | DHT injection in dams post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | [21] | |||
Decreased MMP | Mice | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | JC-1 staining | [20] | ||
Rat | DHEA injection (interscapular region) | 20 days | Rat-to-mouse BAT xenotransplant increased MMP | [24] | |||
Mice – offspring | DHT injection in dams post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | [21] | ||||
ROS & Repair | Increased ROS | Rat | DHEA injection (interscapular region) | 20 days | ROS assay using DCFH-DA | Rat-to-mouse BAT xenotransplant decreased ROS level | [24] |
Human | EVs isolated from PCOS patients with non-hyperandrogenic phenotype were co-cultured with control murine oocytes | DCHF-DA staining | [22] | ||||
Mice – offspring | DHT injection in dams post coitus, assessed post pubertal pup oocytes | GD 16.5, 17.5, 18.5 | CellROX staining | [21] | |||
No differences in ROS | Mice | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | [20] | |||
No differences in lipid peroxidation | Mice | Controlled-release DHT pellet implant | 90 days (2.75μg/day) | BODIPYC11® 581/591 staining | [20] | ||
Increased CAT | Human | EVs isolated from PCOS patients with non-hyperandrogenic phenotype were co-cultured with control murine oocytes | qPCR | [22] | |||
Increased GSS | Human | EVs isolated from PCOS patients with non-hyperandrogenic phenotype were co-cultured with control murine oocytes | qPCR | [22] |
Mitochondrial Function | Effect of PCOS on Mitochondrial Function | Model/ Species | PCOS Model/ Diagnosis | Treatment timeframe | Method | Reference | Therapeutic Intervention | Reference |
---|---|---|---|---|---|---|---|---|
Biogenesis | Increased PGC-1α | Mouse | SQ DHEA | 20 days | WB | [1] | ||
No change in PGC-1α | Rat | IP DHT+INS | GD 0.5 - GD 13.5 | qPCR | [2] | |||
Decreased PGC-1α | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | |||
Increased TFAM | Human | Rotterdam Criteria | WB | [4] | ||||
No change in TFAM | Rat | IP DHT+INS | GD 7.5 - GD 13.5 or GD 14.5 | qPCR | [2,3] | |||
Decreased NRF1 | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | |||
Mitochondrial Genome | Decreased mtDNA copy number | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | ||
Ultrastructure | Decreased TOMM20 | Mouse | SQ DHEA | 20 days | IHC | [1] | L-carnitine/acetyl-L-carnitine returned levels closer to control | [1] |
Increased prohibitin I | Rat | IP DHT+INS | GD 7.5 - GD 14.5 | WB | [5] | |||
Shrunken mitochondria | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | TEM | [6] | |||
Swollen mitochondria | Rat | IP DHT+INS | GD 7.5 - GD 13.5 or GD 14.5 | TEM | [2,5] | N-acetyl-cysteine improved but didn't fully rescue morphology but also impaired mitochondria in controls; flutamide decreased number of small swollen mitochondria but cristae remained disorganized | [2,5] | |
Electron dense and collapsed cristae | Rat | IP DHT+INS | GD 7.5 - GD 13.5 or GD 14.5 | TEM | [2,5,6] | |||
Metabolism | No difference in VDAC | Rat | IP DHT+INS | GD 7.5 - GD 14.5 | WB | [5] | N-acetyl-cysteine didn't change VDAC but did decrease it in controls | [5] |
Decreased Complex I | Rat | IP DHT+INS | GD 7.5 - GD 14.5 | WB | [5] | N-acetyl-cysteine normalized | [5] | |
Increased Complex I | Rat | IP DHT+INS | GD 0.5 - GD 13.5 | WB | [2] | Flutamide normalized | [2] | |
Increased Complex II | Rat | IP DHT+INS | GD 0.5 - GD 13.5 | WB | [2] | Flutamide normalized | [2] | |
Decreased Complex III | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | WB | [3,5] | N-acetyl-cysteine normalized | [5] | |
No difference in PDH | Human | Rotterdam Criteria | WB | [4] | ||||
Dynamics | Decreased DRP1 (Fission) | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | ||
No change in MFN1 (Fusion) | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | |||
No change in OPA1 (Fusion) | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | qPCR | [3] | |||
ROS and Repair | Increased 4-HNE adducts | Mouse | SQ DHEA | 20 days | IHC | [1] | L-carnitine/acetyl-L-carnitine returned levels closer to control | [1] |
Reduced ROS levels | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | OxiSelect In Vitro ROS/RNS assay | [3] | |||
Reduced GPX4 | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | WB, IHC | [6] | |||
Reduced glutathione | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | Glutathione/ glutathione + glutathione disulfide assay | [6] | |||
Reduced phosphorylated SOD1 | Rat | IP DHT+INS | GD 7.5 - GD 13.5 | WB | [3] | |||
Increased SOD2 | Mouse | SQ DHEA | 20 days | WB | [1] | Propionyl-L-carnitine altered levels | [1] |
Mitochondrial Function | Effect of PCOS on Mitochondrial Function | Treatment timeframe | Method | Therapeutic Intervention | Reference |
---|---|---|---|---|---|
Biogenesis | Decreased PGC-1α | GD 7.5 - GD 13.5 | qPCR | [80] | |
Decreased TFAM | GD 7.5 - GD 13.5 | qPCR | [80] | ||
Decreased NRF1 | GD 7.5 - GD 13.5 | qPCR | [80] | ||
Mitochondrial Genome | Decreased mtDNA copy number | GD 7.5 - GD 13.5 | qPCR | [80] | |
Ultrastructure | Mitochondrial blebbing | GD 7.5 - GD 13.5 and GD 14.5 | TEM | [80,81,89] | |
Lack of tubular cristae | GD 7.5 - GD 13.5 or GD 14.5 | TEM | [81,89] | ||
Decreased intracristal dilatation | GD 7.5 - GD 13.5 | TEM | [80] | ||
Morphology changes limited to junctional zone; little change in the labyrinth zone | GD 7.5 - GD 13.5 or GD 14.5 | TEM | High dose NAC abolished damaged morphology in junctional zone but had no effect in labyrinth zone | [81,89] | |
Metabolism | No change in Complex III expression | GD 7.5 - GD 14.5 | WB | Low dose NAC decreased Complex I abundance | [81] |
Decreased VDAC | GD 7.5 - GD 14.5 | WB | High dose NAC increased VDAC abundance | [80,81] | |
Dynamics | Decreased MFN1 (Fusion) | GD 7.5 - GD 13.5 | qPCR | [80] | |
Decreased DRP1 (Fission) | GD 7.5 - GD 13.5 | qPCR | [80] | ||
ROS and Repair | Increased ROS | GD 7.5 - GD 13.5 | OxiSelect In Vitro, ROS/RNS assay | [80] | |
Increased MDA | GD 7.5 - GD 13.5 | MDA ELISA | [80] | ||
Increased cytosolic NRF2 and decreased nuclear NRF2 in basal zone | GD 7.5 - GD 13.5 | WB, IHC | [80] | ||
Reduced phosphorylated SOD1 and p-SOD1:SOD1 ratio | GD 7.5 - GD 13.5 | WB | [80] | ||
No difference in SOD2 abundance | GD 7.5 - GD 13.5 | WB | [80] | ||
No difference in GPX4 abundance | GD 7.5 - GD 13.5 | WB | [89] | ||
Less GPX4 in junctional and labyrinth zones | GD 7.5 - GD 13.5 | IHC | [89] | ||
No GPX4 in nuclei of spongiotrophoblasts, cytotrophoblasts, and synctiotrophoblasts | GD 7.5 - GD 13.5 | IHC | [89] | ||
No difference in glutathione | GD 7.5 - GD 13.5 | Glutathione/ glutathione + glutathione disulfide assay | [89] |
Mitochondrial Function | Effect of PCOS on Mitochondrial Function | Method | Therapeutic Intervention | Reference |
---|---|---|---|---|
Biogenesis | Reduced "GG"(WT) frequency of PGC-1α rs8192678 polymorphism | PCR, RFLP Analysis | [90] | |
No difference in TFAM genotype or allele frequency | PCR, RFLP Analysis | [90] | ||
Mitochondrial Genome | Lower mtDNA copy number | qPCR | [92,93,94] | |
Higher mtDNA copy number | qPCR | [91] | ||
Negative association between mtDNA copy number and fasting insulin, HOMA-IR, waist circumference, and triglycerides | Pearson correlation coefficient | [94] | ||
Positive association between mtDNA copy number and quantitative insulin-sensitivity check index (QUICKI) and sex hormone binding globulin (SHBG) | Pearson correlation coefficient | [94] | ||
No correlation between mtDNA copy number and anthropometric measure nor 8-OHdG | qPCR, 8OH-dG ELISA kit | Metformin decreased mtDNA copy number at 6 and 12 months of treatment | [95] | |
Higher mtDNA4977 deletion rate | qPCR | [91] | ||
Higher frequency of a 9bp deletion | qPCR | [49,96,97,98,99] | ||
ND5 gene polymorphisms: T12811C, T12338C | qPCR | [97,100,101] | ||
A6 gene polymorphisms: G8584A, C8684T | qPCR | [97,98,100] | ||
Unique tRNA variants and higher frequency of variants for Cys and Leu tRNAs | qPCR | [92,97,100] | ||
Greater frequency of D-loop SNPs C150T, T146C, A189G, and D310 | PCR, Mitomap and mtDB mitochondria databases | [49,93] | ||
Carriers of AA genotype of PGC1a polymorphism rs8192678 and D-loop SNPs A189G and D310 had lower mtDNA | PCR, Mitomap and mtDB mitochondria databases | [90,93] | ||
Ultrastructure | No Reports | |||
Metabolism | No Reports | |||
Dynamics | No Reports | |||
ROS and Repair | Decreased PRX3 2-3h post-OGTT | ELISA | [103] | |
Positive correlation between PRX3 at 2h post-OGTT and insulin at 1h post-OGTT | Spearman correlation analysis | [103] |
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