Table 2.
Summary of studies investigating the relationship between expression levels of testicular, spermatozoal, and seminal fluidal miRNAs and idiopathic male infertility in humans
| Study group (sample size) and Type of analyzed samples |
Brief results and miRNAs displaying the greatest fold changes | Reference |
|---|---|---|
| Patients with NOA (3) Testicular tissues |
154 downregulated miRNAs such as miR-17-92 and miR-371/2/3 clusters, miR-1, miR-181a, miR-221, miR-9*, miR-145, miR-383, let-7f, let-7f-2*, let-7i*, miR-19a, miR-20b, miR-29c, miR-30a*, miR-30d*, miR-34b*, miR-449a, miR-652, miR-92a
17 up-regulated miRNAs: miR-129-5p, miR-193a-3p, miR-193a-5p, miR-554, miR-423-3p, miR-491-3p, miR-557, miR-210, miR-23a, miR-302a, miR-371-5p, miR-374a, miR-654-5p, miR-663, miR-638, miR-572, miR-744 |
[99] |
| Patients with azoospermia and oligozoospermia (490) Genomic DNA |
A SNP in the 3’UTR of HIWI2 gene (rs508485T > C) exhibited a significantly increased oligozoospermia risk, whereas HIWI3 variant rs11703684C > T displayed a significantly reduced oligozoospermia risk. | [100] |
| Patients with azoospermia (266) or severe oligozoospermia (228) Genomic DNA |
A SNP (rs6631A > T) in CGA encoding glycoprotein hormone α-subunit resulted in decreased binding affinity of miR-1302 and overexpression of CGA in vitro, and is associated with increased risk for idiopathic male infertility. | [101] |
| Patients with NOA (118), asthenozoospermia (137) and oligoospermia (34) Seminal plasma |
7 miRNAs (miR-34c-5p, miR-122, miR- 146b-5p, miR-181a, miR-374b, miR-509–5p and miR-513a-5p) were found to be markedly decreased in azoospermia but increased in asthenozoospermia. | [102] |
| Patients with NOA (48) and oligozoospermia (48) Seminal plasma |
Expression levels of miR-19b and let-7a in both seminal plasmas and testicular tissues (n = 5) were significantly increased in idiopathic infertile males with NOA. No significant differences were found between the fertile controls and infertile males with oligozoospermia. | [103] |
| Infertile normospermic, oligozospermic and asthenospermic men (667) Genomic DNA |
SNPs in the 3’UTR (rs10719T > C and rs642321C > T) and promoter (rs12323635T > C) regions of Dicer1 were found to be significantly associated with oligozoospermia, and were proposed to result in global changes in miRNA processing through affecting Dicer1 expression levels. | [104] |
| Patients with NOA (100) Seminal plasma |
miR-141, miR-429 and miR-7-1-3p were significantly upregulated in NOA compared to fertile controls. | [129] |
| Patients with asthenozoospermia (9) and oligoasthenozoospermia (9) Spermatozoa |
50 miRNAs upregulated (such as miR-30a, miR-363, miR-26a, miR-200a, miR-141, miR-429, miR-193b, miR-29a, miR-1274a, miR-24, miR-4286, miR-99a) and 27 miRNAs downregulated (such as miR-34b, miR-122, miR-1973) in asthenozoospermic males 42 miRNAs upregulated (such as miR-141, miR-193b, miR-26a, miR-200c, miR-29a, miR-429, miR-200a, miR-99a, miR-363) and 44 miRNAs downregulated (such as miR-34b*, miR-34b, miR-34c-5p, miR-15b, miR-122, miR-449a, miR-1973, miR-16, miR-19a) in oligoasthenozoospermic males. |
[105] |
| Normozoospermic fertile men (10) Spermatozoa |
221 miRNAs were found to be consistently present in all individuals. 48 miRNA pairs displayed a stable expression. miR-532-5p, miR-374b-5p and miR-564 were the best normalizing miRNA candidates, and were proposed to be used as fertility biomarkers. | [98] |
| Oligospermic infertile patients (43) Spermatozoa |
mir-100 and let-7b levels were significantly higher, and ERα (estrogen receptor α) expression was significantly decreased in oligospermic groups. | [106] |
| Oligospermic infertile men (43) Spermatozoa |
mir-21 and mir-22 levels were significantly higher, and ERβ (estrogen receptor β) expression was significantly decreased in oligospermic males. | [13] |
| Azoospermic men (40): SCO (12), MA (12) and GCA (16) subgroups Testicular tissues |
197, 68, and 46 miRNAs were found to be differentially expressed in SCO, MA and GA groups, respectively. | [107] |
| SCO down | miR-34b*, miR-34c-5p, miR-449a, miR-574–5p, miR-15b, miR-125b, miR-125a-5p, miR-16, miR-204, miR-1260, miR-23a, miR-145, miR-1260b, miR-30b, miR-25, miR-1274a, miR-22, miR-34b, miR-19a, miR-574–3p, miR-92a | |
| SCO up | miR-3925, miR-135a*, miR-1471, miR-642b, miR-617, miR-3180–3p, miR-718, miR-3200–5p, miR-99b*, miR-3945, miR-3648, miR-575, miR-936, miR-3137, miR-548q, miR-4322, miR-1181, miR-125a-3p, miR-371–5p, miR-373*, miR-3197, miR-3656, miR-3194 | |
| MA down | miR-34c-5p, miR-34b*, miR-449a, miR-509–5p, miR-514, miR-34b, miR-517a, miR-506, miR-514b-5p, miR-129–3p | |
| MA up | miR-127–3p, miR-410, miR-199a-5p, miR-379 | |
| GCA down | miR-449a, miR-34b*, miR-34c-5p, miR-34b, miR-449b* | |
| GCA up | miR-135a*, miR-3137, miR-99b*, miR-3692* | |
| Patients with oligoospermia / oligoasthenozoospermia (80) and NOA (40) Spermatozoa and testicular tissues |
miR-429 was significantly increased, whereas miR-34b*, miR-34b, miR-34c-5p and miR-122 were decreased in both tested groups compared to normal control subjects. | [108] |
| Infertile men of various subgroups (30) Genomic DNA |
Two allele-specific methylation-sensitive SNPs in PIWIL1 and PIWIL2, rs10773767 and rs6982089 respectively, were found to be associated with idiopathic male infertility. | [109] |
| Azoospermic men with SCO (5) Testicular tissues |
miR-34c-5p, miR-126, miR-191, miR-10b, miR-202-5p, miR-103, miR-514, miR-204 expressions were markedly reduced in testicular tissues from SCO men compared to normal fertile men. | [110] |
| Infertile men with high sperm DNA damage (94) Seminal plasma |
miR-424 was found to be significantly downregulated in the study group compared to the control group. | [111] |
SCO Sertoli cell only, NOA non-obstructive azoospermia, MA mixed atrophy, GCA germ cell arrest