Table 1 Studies on differential expression of miRNAs in male infertility

Halima et al. [66]

12 SCOS (Sertoli cell only syndrome),

12 MA (Mixed atrophy),

16 GA (Germ cell arrest) patients and 16 NC (Normal Control)

Testicular biopsy

Microarray

About 197, 68, and 46 differentially expressed miRNAs were found in SCOS (Sertoli cell only syndrome), MA (Mixed atrophy), GA (Germ cell arrest) patients, respectively as compared to controls. hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p, and hsa-miR-449a were highly upregulated in SCOS, MA, GA patients compared with fertile control.

Lian et al. [65]

3 non-obstructive azoospermic and 2 fertile controls

Testicular biopsy

Microarray

A total of 154 differentially down-regulated and 19 up-regulated miRNAs in non-obstructive azoospermic patients compared with fertile controls. Differential expression of miR-302a, miR-491-3p, miR-520d-3p and miR-383 was confirmed by qRT-PCR.

Noveski et al. [68]

27 hypospermatogenesis, 3 hypospermatogenesis with AZFc deletion,

8 SCOS and 2 MA,

6 normal spermatogenesis

Testicular biopsy

Microarray

A total of 58 differentially expressed miRNAs.

miR-34b, mir-449b, mir-517c were downregulated in all studied groups compared with control.

Zhang et al. [69]

13 non-obstructive azoospermic and

6 fertile controls

Testicular biopsy

Microarray

One hundred twenty-nine miRNAs were found to be differentially expressed in testicular tissues of non-obstructive azoospermic patients as compared to controls. Combination of two miRNAs (miR-10b-3p and miR-34b-5p) showed to have potential biomarker of azoospermia.

Yao et al. [12]

60 non-obstructive azoospermic and 20 obstructive azoospermic

Spermatogonia, pachytene spermatocytes, and round spermatids

Illumina HiSeq 2000

 A total of 396, 395, 378 miRNAs were differentially expressed in spermatogonia, spermatocyte and spermatid, respectively in non-obstructive azoospermic compared to obstructive azoospermic patients.

Piryaei et al. [70]

10 non-obstructive azoospermic and

8 obstructive azoospermic

Testicular biopsy

BGISEQ-500 platform

About 120 downregulated and 10 upregulation miRNAs in non-obstructive azoospermic cases compared to obstructive azoospermic. hsa-miR-449a, hsa-miR-34c-3p, hsa-miR-375, hsa-miR-517b-3p, hsa-miR-512-3p, hsa-miR-34c-5p, hsa-miR-520c-3p, hsa-miR-516b-5p, hsa-miR-1323, hsa-miR-34b-3p are top 10 downregulated miRNAs.

Wu et al. [8]

48 non-obstructive azoospermic and 48 fertile controls

Seminal plasma

qRT-PCR

miR-19b and let-7a found to be up-regulated in non-obstructive azoospermic patients compared to fertile controls.

Wu et al. [76]

100 non-obstructive azoospermic and 100 fertile controls

Seminal plasma

qRT-PCR

miR-141, miR-429 and miR-7-1-3p found to be significantly upregulated in non-obstructive azoospermic compared with fertile controls.

Barcelo et al. [77]

14 non-obstructive azoospermic, 13 obstructive azoospermic and

9 normozoospemic

Extracellular vesicles (sEVs) of seminal fluid

miRNA quantitative PCR panels

Sixty DE miRNAs in infertile patients compared with normozoosperic controls.

miR-31-5p was identified as potential predictor of azoospermia.

Zhang et al. [78]

7 SCOS (Sertoli cell only syndrome),

6 hypospermatogenesis and 7 fertile controls

Seminal plasma

Illumina HiSeq 2000

78 miRNAs to be up-regulated and 132 miRNAs to be down-regulated in patients with SCOS (Sertoli cell only syndrome) pateints as compared to fertile controls, whereas 32 were up-regulated and 90 were down-regulated in patients with SA (spermatogenic arrest) patients in comparison to fertile controls.

Cito et al. [103]

14 non-obstructive azoospermic and

10 controls

Blood

qRT-PCR

Upregulated level of miR-20a-5p in non-obstructive azoospermic patients compared with fertile controls.

Naeimi et al. [104]

103 infertile men and

121 fertile control

Blood

qRT-PCR

miR-211 found to be downregulated in infertile men compared to the control.

Trzybulska et al. [105]

79 subfertile and 38 fertile controls

Serum

qRT-PCR

Serum miRNAs (miR-155-5p and miR-200c-3p potential biomarker for subfertility.

Liu et al. [9]

86 infertile and 86 fertile controls

Sperm

Microarray

About 56 downregulated miRNAs

miR-574-5p, miR-297, miR-122, miR-1275, miR-373, miR-185, miR-193b were up-regulated and miR-100, miR-512-3p, miR-16, miR-19b, miR-23b and miR-26a were found in infertile males as compared to fertile males.

Abu-Halima et al. [89]

9 obstructive azoospermic, 9 azoospermic and

9 normozoospermic controls

Sperm

Microarray

Fifty miRNAs up-regulated and 27 miRNAs down-regulated in asthenozoospermic males. In oligoasthenozoospermic males, 42 miRNAs were up-regulated and 44 miRNAs down-regulated when compared with normozoospermic males.

Munoz et al. [90]

9 oligozoospermic and 7 normozoospermic fertile controls

Sperm

qRT-PCR

About 12 miRNAs were up-regulated (let-7b, -7c, -7 g, miR-21, -22, -30a, -148a, -221, -320a, -375, -423-3p, -423-5p) and 6 miRNAs were down-regulated (miR-25, -34b, -122, -152, -192, and 335) in oligozoopermic patients as compared to controls.

Mokánszki et al. [91]

10 oligozoospermic,

10 asthenozoospermic and

10 fertile controls

Sperm

qRT-PCR

Five miRNAs (let-7a, miR-7-1-3p, -141, -200a, -429) were significantly up-regulated and 3 miRNAs (miR-15b, miR34b, miR-122) were significantly down-regulated in the infertile group compared to the fertile group.

Salas-Huetos et al. [92]

10 asthenozoospermic,

10 teratozoospermic,

10 oligozoospermic and

10 fertile controls

Sperm

qRT-PCR

A total of 32, 19 and 18 differentially expressed miRNAs in asthenozoospermic, teratozoospermic and oligozoospermic men, respectively, as compared to controls

Salas-Huetos et al. [93]

8 normozoospermic infertile and 10 normozoospermic fertile

Sperm

qRT-PCR

Fifty-seven miRNAs were differentially expressed miRNA including

45 up- and 12 down-expressed miRNAs.

Abu-Halima et al. [94]

80 sub fertile and 90 fertile controls

Sperm and testicular biopsies.

qRT-PCR

hsa-miR-429 was found to be upregulated whereas hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p and hsa-miR-122 downregulated in spermatogenic disruption.

Vazquez et al. [95]

10 asthenozoospermic,

10 teratozoospermic,

10 oligozoospermic and

10 fertile controls

Sperm

qRT-PCR

hsa-miR-942-5p/hsa-miR-1208 and hsa-miR-34b-3p/hsa-miR-93-3p showed the greatest potential for detecting seminal alterations in infertile cohort.

Abhari et al. [98]

43 oligozoospermic and 43 fertile controls

Sperm

qRT-PCR

miR-21, miR-22 levels were significantly higher in oligozoospermic than those in normal controls.

Heidary et al. [99]

39 azoospermic and 35 fertile controls

Sperm

Solexa sequencing

Eighteen significantly altered miRNAs in azoospermic men in comparison to controls. Seven miRNAs (miR-1‐3p, miR‐197‐3p, miR‐296‐5p, and miR‐625‐3p, miR‐328‐3p, miR‐888‐3p and miR‐92b‐3p) validated by RT-PCR and miR-888-3p found to be significantly overexpressed in azoospermic cases in comparison with controls.

Liang et al. [101]

4 asthenozoospermic and

3 control males

Sperm

Microarray

Sixteen significantly differentially expressed miRNAs were identified. miR-6739 and miR34-5p were highly differentially expressed miRNAs.