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Table 1 Potential biomarkers found in follicular fluid extracellular vesicles (exosome-like vesicles) from patients with polycystic ovarian syndrome

From: Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Types of molecule

Potential biomarker(s)

Comparision

EV isolation method

EV characterization techniques

Detection technique

Sample size

Total number differentially expressed

Reference

Year of publication

Complete reference

lncRNAs

↑ AC073140.1, AC007614.1, CDC42-AS1

↓ AC027020.2

Lean PCOS v. Lean non-PCOS

Differential centrifugation and Exoquick precipitation

NTA

RNASeq

20

3 upregulated

1 downregulated

PMID: 37,404,312

2023

Wyse BA, Salehi R, Russell SJ, Sangaralingam M, Jahangiri S, Tsang BK, Librach CL. Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles. Front Endocrinol (Lausanne). 2023 Jun 19;14:1,205,385. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fendo.2023.1205385. PMID: 37,404,312; PMCID: PMC10315679

miRNAs

↑ miR-509-3p, miR-3655-5p, miR-30a-5p

Lean PCOS v. Lean non-PCOS

Differential centrifugation and Exoquick precipitation

NTA

RNASeq

20

6 upregulated

0 downregulated

PMID: 37,404,312

2023

Wyse BA, Salehi R, Russell SJ, Sangaralingam M, Jahangiri S, Tsang BK, Librach CL. Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles. Front Endocrinol (Lausanne). 2023 Jun 19;14:1,205,385. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fendo.2023.1205385. PMID: 37,404,312; PMCID: PMC10315679

lncRNAs

↑ AC092944.1, AC007848.1, AC114811.2

↓ CRNDE, CDC42-AS1

Obese PCOS v. Obese non-PCOS

Differential centrifugation and ExoQuick precipitation

NTA

RNASeq

15

8 upregulated

2 downregulated

PMID: 37,404,312

2023

Wyse BA, Salehi R, Russell SJ, Sangaralingam M, Jahangiri S, Tsang BK, Librach CL. Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles. Front Endocrinol (Lausanne). 2023 Jun 19;14:1,205,385. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fendo.2023.1205385. PMID: 37,404,312; PMCID: PMC10315679

miRNAs

↑ miR-6500-3p

↓ miR-3655-5p

Obese PCOS v. Obese non-PCOS

Differential centrifugation and ExoQuick precipitation

NTA

RNASeq

15

1 upregulated

1 downregulated

PMID: 37,404,312

2023

Wyse BA, Salehi R, Russell SJ, Sangaralingam M, Jahangiri S, Tsang BK, Librach CL. Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles. Front Endocrinol (Lausanne). 2023 Jun 19;14:1,205,385. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fendo.2023.1205385. PMID: 37,404,312; PMCID: PMC10315679

miRNAs

↓ miR-379-5p

PCOS v. Normal

Differential centrifugation and ExoQuick precipitation

NTA,WB

qPCR

38

N/A

PMID: 37,033,997

2023

Salehi R, Asare-Werehene M, Wyse BA, Abedini A, Pan B, Gutsol A, Jahangiri S, Szaraz P, Burns KD, Vanderhyden B, Li J, Burger D, Librach CL, Tsang BK. Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome. Front Immunol. 2023 Mar 24;14:1,104,550. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fimmu.2023.1104550. PMID: 37,033,997; PMCID: PMC10081157

miRNAs

↑ miR-3131, mir-206, miR-204-5p

↓ miR-539-5p, miR-379-3p, miR-655-3p

PCOS v. Normal

Ultracentrifugation

TEM, NTA, WB

RNASeq

6

267 upregulated

247 downregulated

PMID: 36,695,944

2023

Yang Y, Lang P, Zhang X, Wu X, Cao S, Zhao C, Shen R, Ling X, Yang Y, Zhang J. Molecular characterization of extracellular vesicles derived from follicular fluid of women with and without PCOS: integrating analysis of differential miRNAs and proteins reveals vital molecules involving in PCOS. J Assist Reprod Genet. 2023 Mar;40(3):537–552. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s10815-023-02724-z. Epub 2023 Jan 25. PMID: 36,695,944; PMCID: PMC10033803

proteins

↑ GSTM2, SAMD9L, CDHR2

↓ DHCR7, NSDHL, IGKC

PCOS v. Normal

Ultracentrifugation

TEM, NTA, WB

Tandem mass tagging (TMT)

6

9 upregulated

23 downregulated

PMID: 36,695,944

2023

Yang Y, Lang P, Zhang X, Wu X, Cao S, Zhao C, Shen R, Ling X, Yang Y, Zhang J. Molecular characterization of extracellular vesicles derived from follicular fluid of women with and without PCOS: integrating analysis of differential miRNAs and proteins reveals vital molecules involving in PCOS. J Assist Reprod Genet. 2023 Mar;40(3):537–552. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s10815-023-02724-z. Epub 2023 Jan 25. PMID: 36,695,944; PMCID: PMC10033803

miRNAs

↑ miR-143-3p

↓ miR-155-5p

PCOS v. Normal

Qiagen exoEasy

TEM, NTA, WB

RNASeq

12

44 upregulated

39 downregulated

PMID: 35,534,864

2022

Cao J, Huo P, Cui K, Wei H, Cao J, Wang J, Liu Q, Lei X, Zhang S. Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome. Cell Commun Signal. 2022 May 9;20(1):61. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12964-022-00876-6. Erratum in: Cell Commun Signal. 2022 Aug 1;20(1):116. PMID: 35,534,864; PMCID: PMC9082924

miRNAs

↑ miR-3960

↓ miR-424-5p, miR-377-3p, miR-10_21456

PCOS v. Normal

ExoQuick precipitation

TEM, NTA, WB

Microarray

8

19 upregulated

6 downregulated

PMID: 33,930,499

2021

Yuan D, Luo J, Sun Y, Hao L, Zheng J, Yang Z. PCOS follicular fluid derived exosomal miR-424-5p induces granulosa cells senescence by targeting CDCA4 expression. Cell Signal. 2021 Sep;85:110,030. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.cellsig.2021.110030. Epub 2021 Apr 28. PMID: 33,930,499

miRNA

qRT-PCR:

↑ miR-3148, miR-4271, miR-3646, miR-3976, miR-4481, miR-34a-5p, miR-15b-5p

PCOS v. Normal

ExoQuick precipitation

TEM, WB

Microarray

60

27 upregulated

41 downregulated

PMID: 33,840,620

2021

Cui C, Wang J, Han X, Wang Q, Zhang S, Liang S, Li H, Meng L, Zhang C, Chen H. Identification of small extracellular vesicle-linked miRNA specifically derived from intrafollicular cells in women with polycystic ovary syndrome. Reprod Biomed Online. 2021 May;42(5):870–880. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.rbmo.2021.02.002. Epub 2021 Feb 8. PMID: 33,840,620

lncRNAs

↑ H19, POP4, DICER, PTEN, AKT3, HDAC6

PCOS v. Normal

Differential centrifugation and total exosome isolation reagent

None

RNASeq

6

1253 upregulated

613 downregulated

PMID: 33,679,867

2021

Wang L, Fan H, Zou Y, Yuan Q, Hu X, Chen X, Zhu C, Zhang X, Cui H. Aberrant Expression of Long Non-coding RNAs in Exosomes in Follicle Fluid From PCOS Patients. Front Genet. 2021 Feb 17;11:608,178. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fgene.2020.608178. PMID: 33,679,867; PMCID: PMC7925891

miRNAs

↑ miR-200c-3p, miR-10a-5p, miR-100-5p

↓ miR-17-5p

PCOS v. Oocyte donors

Size exclusion chromatography

TEM, NTA, WB

RNASeq

15

0 in EVs, 5 upregulated and 5 downregulated in EV free FF, and 17 upregulated and 13 downregulated in GCs

PMID: 33,333,986

2020

Rooda I, Hasan MM, Roos K, Viil J, Andronowska A, Smolander OP, Jaakma Ü, Salumets A, Fazeli A, Velthut-Meikas A. Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries. Int J Mol Sci. 2020 Dec 15;21(24):9550. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/ijms21249550. PMID: 33,333,986; PMCID: PMC7765449

miRNAs

↑ miR-6087, miR-4745-3p, miR-193b-3p

↓ miR-200c-3p, miR-3911, miR-141-3p

PCOS v. Normal

Ultracentrifugation

TEM, Flow cytometry

RNASeq

4

Selected 10 upregulated and 10 downregulated

PMID: 32,117,643

2020

Hu J, Tang T, Zeng Z, Wu J, Tan X, Yan J. The expression of small RNAs in exosomes of follicular fluid altered in human polycystic ovarian syndrome. PeerJ. 2020 Feb 19;8:e8640. https://doiorg.publicaciones.saludcastillayleon.es/10.7717/peerj.8640. PMID: 32,117,643; PMCID: PMC7035867

piRNAs

↑ piR_004506, piR_019068, piR_013624

↓ piR_022506, piR_015800, piR_008113

PCOS v. Normal

Ultracentrifugation

TEM, Flow cytometry

RNASeq

4

Selected 10 upregulated and 10 downregulated

PMID: 32,117,643

2020

Hu J, Tang T, Zeng Z, Wu J, Tan X, Yan J. The expression of small RNAs in exosomes of follicular fluid altered in human polycystic ovarian syndrome. PeerJ. 2020 Feb 19;8:e8640. https://doiorg.publicaciones.saludcastillayleon.es/10.7717/peerj.8640. PMID: 32,117,643; PMCID: PMC7035867

tRNA

↑ trna12-ValAAC, trna152-ValCAC, trna5-GluTTC

↓ trna116-GluCTC, trna4-GluCTC, trna74-GluCTC

PCOS v. Normal

Ultracentrifugation

TEM, Flow cytometry

RNASeq

4

Selected 10 upregulated and 10 downregulated

PMID: 32,117,643

2020

Hu J, Tang T, Zeng Z, Wu J, Tan X, Yan J. The expression of small RNAs in exosomes of follicular fluid altered in human polycystic ovarian syndrome. PeerJ. 2020 Feb 19;8:e8640. https://doiorg.publicaciones.saludcastillayleon.es/10.7717/peerj.8640. PMID: 32,117,643; PMCID: PMC7035867