. 2023 Aug 23;24(17):13123. doi: 10.3390/ijms241713123

Table 1.

Effects of PCOS on mitochondrial function in the ovary.

Mitochondrial Function	Effect of PCOS Condition on Mitochondrial Function	Model—Species	PCOS Model/Diagnosis	Treatment Timeframe	Method	Therapeutic Intervention	Reference
Biogenesis	Decreased PGC1 $α$	Rat	IP Letrozole + HFD	21 days, 21 days, 35 days, 12 weeks	qPCR, WB	Cangfudaotan (IG) and metformin (IG) increased PGC1 $α$ to control levels	[52]
		Rat	IG Letrozole	21 days	WB		[53]
		Mouse	SQ DHT	35 days	WB	Overexpressing SIRT3 in vivo increased PGC1 $α$ back to control levels	[56]
		Mouse	HF/HGD (58% kcal fat + sucrose)	12 weeks	qPCR	Neurokinin-B antagonist increased PGC1 $α$ back to control levels	[54]
	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	[55]
		Rat	IG Letrozole	21 days	WB		[53]
		Mouse	HF/HGD (58% kcal fat + sucrose)	12 weeks	qPCR	Neurokinin-B antagonist increased TFAM back to control levels	[54]
	Decreased NRF1	Mouse	HF/HGD (58% kcal fat + sucrose)	12 weeks	qPCR	Neurokinin-B antagonist increased NRF1 back to control levels	[54]
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	[52]
Ultrastructure	Membrane swelling and ruptures	Rat	IP Letrozole + HFD	21 days	EM	% of total damaged mitochondria decreased with either metformin (IG) or cangfudaotan (IG) but were still higher than control levels	[52]
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		[58]
	Decreased OCR, RCR	Rat	IP letrozole + HFD	21 days	Oxytherm Clark-type electrode on isolated mitochondria	Cangfudaotan (IG) increased OCR, RCR	[52]
	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)	[57]
	Decreased ATP	Rat	IP letrozole + HFD	21 days	ATP assay	Cangfudaotan (IG) increased ATP levels	[52]
	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		[58]
	Decreased activity of mitochondrial complex enzymes	Rat	IP letrozole + HFD	21 days	Complex enzyme activity assays	Cangfudaotan (IG) increased mitochondrial complex activity	[52]
	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)	[57]
	Decreased Complex I activity	Rat	SQ DHEA	20 days	Complex I enzyme activity assay	Bushen Huatan Granules (OG) increased activity of Complex I	[51]
	Decreased Complexes III, IV activity		SQ DHEA	20 days	Complexes III, IV enzyme activity assays	Bushen Huatan Granules (OG) increased activity of Complexes III and IV	[51]
	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		[58]
	Decreased citrate synthase activity	Rat	OG letrozole	21 days	Citrate synthase activity assay	Metformin (OG) and sodium selenite (OG) increased mitochondrial citrate synthase activity but still lower than control group	[59]
	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)	[57]
	Decreased MMP	Rat	IP letrozole + HFD	21 days	JC-1 staining	Cangfudaotan (IG) or metformin (IG) increased MMP	[52]
Dynamics	Decreased MFN1	Rat	IP letrozole + HFD	21 days	qPCR/WB	Cangfudaotan (IG) or metformin (IG) increased MFN1	[52]
	Decreased MFN1	Rat	IG Letrozole	21 days	WB		[53]
	Decreased MFN2	Rat	IP letrozole + HFD	21 days	qPCR/WB	Cangfudaotan (IG) or metformin (IG) increased MFN2	[52]
		Rat	OG letrozole (OG)	21 days	qPCR/ELISA kit	Metformin (OG) and sodium selenite (OG) increased MFN2 but still lower than control group	[59]
		Rat	IG Letrozole	21 days	WB		[53]
	Decreased OPA1	Rat	IP letrozole + HFD	21 days	qPCR/WB	Cangfudaotan (IG) or metformin (IG) increased OPA1	[52]
	Increased DRP1	Rat	IP letrozole + HFD	21 days	qPCR/WB	Cangfudaotan (IG) or metformin (IG) decreased DRP1	[52]
		Rat	OG letrozole	21 days	qPCR/ELISA kit	Metformin (OG) and sodium selenite (OG) decreased DRP1 but still higher than control group	[59]
		Rat	IG Letrozole	21 days	WB		[53]
	Increased FIS1	Rat	IP letrozole + HFD	21 days	qPCR/WB	Cangfudaotan (IG) or metformin (IG) decreased FIS1	[52]
	Increased FIS1	Rat	IG Letrozole	21 days	WB		[53]
ROS and Repair	Increased ROS	Rat	IP letrozole + HFD	21 days	DCF staining	Cangfudaotan (IG) or metformin (IG) decreased ROS	[52]
	Increased ROS	Rat	IG Letrozole	21 days	Activity to produce superoxide anion assay		[53]
	Increased mitochondrial superoxide	Rat	SQ DHEA	20 days	MitoSOX staining	Bushen Huatan Granules (OG) decreased mitochondrial superoxide	[51]
	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	[57]
		Rat	OG letrozole	21 days		Metformin (OG) and sodium selenite (OG) decreased lipid peroxidation but still higher than control group	[59]
		Rat	SQ DHEA	21 days			[60]
		Rat	IG Letrozole	21 days			[53]
		Mouse	SQ DHEA	20 days		Genistein decreased lipid peroxidation	[61]
	Increased protein oxidation	Rat	OG letrozole	21 days	DNPH reaction assay	Metformin (OG) and sodium selenite (OG) decreased protein oxidation but still higher than control group	[59]
	Increased DNA oxidation	Mouse	SQ DHEA	20 days	8-OHdG ELISA	Genistein decreased DNA oxidation levels	[61]
	Decreased antioxidant capacity	Rat	OG letrozole	21 days	Ferric-reducing antioxidant power assay	Metformin (OG) and sodium selenite (OG) increased antioxidant capacity but still lower than control group	[59]
	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	[57]
		Rat	SQ DHEA	21 days			[60]
		Mouse	SQ DHEA	20 days		Genistein increased SOD	[61]
	Decreased SOD1	Mouse	HF/HGD (58% kcal fat + sucrose)	12 weeks	qPCR	Neurokinin-B antagonist increased SOD1	[54]
	Increased SOD2 (MnSOD)	Mouse	SQ DHEA	20 days	WB	(1) LC + ACL and (2) LC, ACL + propionyl-L-carnitine both decreased SOD2	[55]
	Increased SOD2 (MnSOD)	Rat	IG Letrozole	21 days	WB		[53]
	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	[57]
	Decreased GSH-Px (GPx)	Rat	OG letrozole	21 days	GPx enzyme activity assay	Metformin (OG) and sodium selenite (OG) increased GPx activity but still lower than control group	[59]
	Decreased GSH-Px (GPx)	Mouse	SQ DHEA	20 days	GSH-Px level	Genistein increased GSH-Px	[61]
	Increased GSH-Px	Rat	IG Letrozole	21 days	GSH-Px enzyme activity assay		[53]
	Decreased GR	Mouse	SQ DHEA	20 days	GR enzyme activity assay		[61]
	Decreased GSH:GSSG ratio	Mouse	SQ DHEA	20 days	GSH and GSSG levels	Genistein increased GSH:GSSG ratio	[61]
	Decreased CAT activity	Mouse	SQ DHEA	20 days	CAT enzyme activity assay	Genistein increased CAT activity	[61]
		Rat	SQ DHEA	21 days	CAT enzyme activity assay		[60]
		Mouse	HF/HGD (58% kcal fat + sucrose)	12 weeks	qPCR	Neurokinin-B antagonist increased CAT expression	[54]
	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	[52]
	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	[51]

Footnotes for Table 1, Table 2 and Table 3: GC: granulosa cell; PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; TFAM: mitochondrial transcription factor A; NRF1: nuclear respiratory factor 1; OCR: oxygen consumption rate; RCR: respiratory control ratio; MMP: mitochondrial membrane potential; MFN1: mitofusin 1; MFN2: mitofusin 2; OPA1: optic atrophy 1 mitochondrial dynamin-like GTPase; DRP1: dynamin-related protein 1; FIS1: fission 1; SOD: superoxide dismutase; SOD1: superoxide dismutase 1; SOD2: superoxide dismutase 2; MnSOD: manganese superoxide dismutase; GSH: reduced glutathione; GSH-Px: glutathione peroxidase; GPx: glutathione peroxidase; GR: glutathione reductase; GSSG: oxidized glutathione; CAT: catalase; mPTP: mitochondrial permeability transition pore; NDUFB8: NADH:Ubiquinone Oxidoreductase Subunit B8; ATP5j: ATP Synthase Peripheral Stalk Subunit F6; VDAC1: voltage-dependent anion-selective channel 1; TSPO: translocator protein; UPR-MT: mitochondrial unfolded protein response; ND1: NADH dehydrogenase 1; ND2: NADH dehydrogenase 2; ND5: NADH dehydrogenase 5; ND6: NADH dehydrogenase 6; CO1: cytochrome c oxidase subunit 1; CO2: cytochrome c oxidase subunit 2; CO3: cytochrome c oxidase subunit 3; IP: intraperitoneal; HFD: high-fat diet; IG: intragastric; SQ: subcutaneous; DHT: dihydrotestosterone; HGD: high-glucose diet; kcal: kilocalories; DHEA: dehydroepiandrosterone; OG: oral gavage; EV: extracellular vesicle; GD: gestational day; EM: electron microscopy; TEM: transmission electron microscopy; XF: extracellular flux analysis; JC-1: mitochondrial membrane potential probe; DCF: Dichlorofluorescein; DCHF-DA: 2′-7′-Dichlorodihydrofluorescein diacetate; MDA: malondialdehyde; BAT: brown adipose tissue; TMRE: Tetramethylrhodamine, ethyl ester; ICC: immunocytochemistry; SIRT3: sirtuin 3; SeNP: selenium nanoparticle; 8-OHdG: 8-hydroxy-2′-deoxyguanosine; si-NK3R: small interfering RNA targeting human NK3R; eCG: equine chorionic gonadotropin.