Coding and regulatory transcriptome comparisons between fertile and infertile spermatozoa identify RNA signatures of male infertility.

The aim of the present study was to identify RNA-based signatures of male infertility by sperm transcriptome analysis. In this study, deep sequencing analyses of coding (mRNA) and regulatory (miRNA) transcriptomes were performed by pooling 15 oligo/oligoasthenozoospermic infertile sperm and 9 normozoospermic fertile sperm samples. Furthermore, interesting candidates were selected for validation by real-time PCR. The comparison of miRNAs between cases and controls identified 94 differentially expressed miRNAs, of which at least 38 have known functions in spermatogenesis. In transcriptome (mRNA) data, a total of 60,505 transcripts were obtained. The comparison of coding RNAs between cases and controls revealed 11,688 differentially expressed genes. miRNA-mRNA paired analysis revealed that 94 differentially expressed miRNAs could potentially target 13,573 genes, of which 6419 transcripts were actually differentially expressed in our data. Out of these, 3303 transcripts showed inverse correlation with their corresponding regulatory miRNAs. Moreover, we found that most of the genes of miRNA-mRNA pairs were involved in male germ cell differentiation, apoptosis, meiosis, spermiogenesis and male infertility. In conclusion, we found that a number of sperm transcripts (miRNAs and mRNAs) have a very high potential of serving as infertility/sperm quality markers.

HCG therapy in azoospermic men with lower or borderline testosterone levels and the prognostic value of Y-deletion analysis in its outcome.

The purpose of this study was to investigate the efficacy of hCG therapy in hypogonadotropic hypogonadic (HH) azoospermic males along with dissecting the prognostic value of Y-deletion analysis in these patients. Fifty-eight azoospermic infertile males with diminished testosterone levels (≤400 ng/dl) and hypogonadism symptoms were subjected to human chorionic gonadotropin (hCG) therapy, and Y-deletion analysis was undertaken. Post-treatment, 43% (25/58) patients showed improvement in sperm count with 8.6% (5/58) turning severe oligozoospermic, 24.14% (14/58) patients turning oligozoospermic and 10.54% (6/58) turning normozoospermic. Among responders, the mean sperm concentration was 8.47 ± 13.16 million/ml, sperm count was 17.05 ± 26.17 million, sperm motility was 52.59% ± 25.09% and sperm progressive motility was 26.91% ± 20.51%. Seventeen out of 25 (68%) responders and 11/33 (33%) nonresponders showed an improvement in libido post-therapy. A Y-deletion was observed in 8% (2/25) responders and in 39.39% (13 out of 33) nonresponders. The Y-deletions were more often found in nonresponders in comparison with the responders (Fisher's exact probability test, p = .007, one tailed). We conclude that hCG therapy in hypogonadotropic azoospermic males is effective in improving andrological parameters and sperm production and that Y-chromosome deletion analysis has prognostic significance in predicting the success of hCG therapy.

AZF deletions in Indian populations: original study and meta-analyses.

PURPOSE: To identify the frequency of Y chromosome microdeletions in Indian populations and to quantitatively estimate the significance of association between these deletions and male infertility. METHODS: A total of 379 infertile males (302 azoospermic and 77 oligozoospermic infertile males) and 265 normozoospermic fertile males were evaluated for Y chromosome microdeletions (YCD) using PCR amplification and gel electrophoresis. Meta-analyses were performed on AZFa (2079 cases and 1217 controls), AZFb (2212 cases and 1267 controls), AZFc (4131 cases and 2008 controls), and AZFb+c (1573 cases and 942 controls) deletions data to quantitatively estimate the significance of association between these deletions and male infertility in Indian populations. RESULTS: The results revealed that out of 379 infertile azoospermic and oligozoospermic males, 38 (10.02%) had AZF deletions. No deletion was found in control samples. The highest percentage of deletions was observed in the AZFc region, followed by AZFa and AZFb. Qualitative analysis showed that AZF deletions were present in 0.59 to 32.62% (average 13.48%) of infertile cases in Indian populations. Meta-analysis revealed a significant association of AZFa (OR = 6.74, p value = 0.001), AZFb (OR = 4.694, p value = 0.004), AZFc (OR = 13.575, p value = 0.000), and AZFb+c (OR = 5.946, p value = 0.018) deletions with male infertility. CONCLUSION: AZF deletions were seen in 10.02% of azoospermic and oligozoospermic cases with the highest frequency of AZFc deletions. Pooled analysis for all studies showed deletion frequency from 0.59 to 32.62% (average = 13.48%). Meta-analysis showed significant association of AZFa, AZFb, and AZFb+c deletions with male infertility. Analysis of Y chromosome microdeletions should be reckoned as an essential testing for diagnostic and therapeutic purposes.