Table 4.

Effects of PCOS on mitochondrial function in the uterus.

Mitochondrial Function	Effect of PCOS on Mitochondrial Function	Model/Species	PCOS Model/Diagnosis	Treatment Timeframe	Method	References	Therapeutic Intervention	References
Biogenesis	Increased PGC-1α	Mouse	SQ DHEA	20 days	WB	[77]
	No change in PGC-1α	Rat	IP DHT + INS	GD 0.5–GD 13.5	qPCR	[78]
	Decreased PGC-1α	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
	Increased TFAM	Human	Rotterdam Criteria		WB	[76]
	No change in TFAM	Rat	IP DHT + INS	GD 7.5–GD 13.5 or GD 14.5	qPCR	[78,79]
	Decreased NRF1	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
Mitochondrial Genome	Decreased mtDNA copy number	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
Ultrastructure	Decreased TOMM20	Mouse	SQ DHEA	20 days	IHC	[77]	L-carnitine/acetyl-L-carnitine returned levels closer to control	[77]
	Increased prohibitin I	Rat	IP DHT + INS	GD 7.5–GD 14.5	WB	[81]
	Shrunken mitochondria	Rat	IP DHT + INS	GD 7.5–GD 13.5	TEM	[82]
	Swollen mitochondria	Rat	IP DHT + INS	GD 7.5–GD 13.5 or GD 14.5	TEM	[78,81]	N-acetyl-cysteine improved but did not fully rescue morphology and also impaired mitochondria in controls; flutamide decreased number of small swollen mitochondria but cristae remained disorganized	[78,81]
	Electron-dense and collapsed cristae	Rat	IP DHT + INS	GD 7.5–GD 13.5 or GD 14.5	TEM	[78,81,82]
Metabolism	No difference in VDAC	Rat	IP DHT + INS	GD 7.5–GD 14.5	WB	[81]	N-acetyl-cysteine did not change VDAC but did decrease it in controls	[81]
	Decreased Complex I	Rat	IP DHT + INS	GD 7.5–GD 14.5	WB	[81]	N-acetyl-cysteine normalized	[81]
	Increased Complex I	Rat	IP DHT + INS	GD 0.5–GD 13.5	WB	[78]	Flutamide normalized	[78]
	Increased Complex II	Rat	IP DHT + INS	GD 0.5–GD 13.5	WB	[78]	Flutamide normalized	[78]
	Decreased Complex III	Rat	IP DHT + INS	GD 7.5–GD 13.5	WB	[79,81]	N-acetyl-cysteine normalized	[81]
	No difference in PDH	Human	Rotterdam Criteria		WB	[76]
Dynamics	Decreased DRP1 (Fission)	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
	No change in MFN1 (Fusion)	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
	No change in OPA1 (Fusion)	Rat	IP DHT + INS	GD 7.5–GD 13.5	qPCR	[79]
ROS and Repair	Increased 4-HNE adducts	Mouse	SQ DHEA	20 days	IHC	[77]	L-carnitine/acetyl-L-carnitine returned levels closer to control	[77]
	Reduced ROS levels	Rat	IP DHT + INS	GD 7.5–GD 13.5	OxiSelect In Vitro ROS/RNS assay	[79]
	Reduced GPX4	Rat	IP DHT + INS	GD 7.5–GD 13.5	WB, IHC	[82]
	Reduced glutathione	Rat	IP DHT + INS	GD 7.5–GD 13.5	Glutathione/glutathione + glutathione disulfide assay	[82]
	Reduced phosphorylated SOD1	Rat	IP DHT + INS	GD 7.5–GD 13.5	WB	[79]
	Increased SOD2	Mouse	SQ DHEA	20 days	WB	[77]	Propionyl-L-carnitine altered levels	[77]

PGC1$\alpha$: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; TFAM: mitochondrial transcription factor A; NRF1: nuclear respiratory factor 1; TOMM20: translocase of the outer membrane; VDAC: voltage-dependent anion channel; PDH: pyruvate dehydrogenase; DRP1: dynamin-related protein 1; MFN1: mitofusin 1; OPA1: optic atrophy 1 mitochondrial dynamin-like GTPase; 4-HNE: 4-hydroxynonenal; GPX4: glutathione peroxidase 4; SOD: superoxide dismutase; SQ: subcutaneous; IP: intraperitoneal; DHEA: dehydroepiandosterone; DHT: dihydrotestosterone; INS: insulin; GD: gestational day; WB: Western blot; IHC: immunohistochemistry; TEM: transmission electron microscopy.