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Inhibin B appears to be the physiological feedback signal for FSH. Herein the determination of serum levels of inhibin B, FSH, LH and testosterone in 148 infertile patients and their association with clinical findings and seminal parameters are reported. A significant negative correlation of FSH and inhibin B (r = -0.60) was found. LH levels showed a significant inverse correlation (r = 0.37), but a weak regression (c0 = 0.01). No correlation with testosterone levels occurred. A significantly positive correlation was observed between testis volume and inhibin levels (r = 0.39) as well as between sperm count and inhibin levels (r = 0.39). To evaluate whether the secretion of inhibin B depends on the nature of damage to the Sertoli cells, inhibin levels in 23 patients with varicocele; eight after cryptorchidism, and 16 after hemiorchiectomy were compared to those of other patients without these diseases, but identical sperm count. No significant differences were found. In 20 men undergoing testicular biopsy, inhibin levels were compared to histology. Although the men with Sertoli-cell-only syndrome had significantly lower levels ((15.83 +/- 12.2) pg ml-1) than those with normal spermatogenesis ((183.8 +/- 112.3) pg ml-1), a distinction between patients with hypospermatogenesis from those with normal spermatogenesis was not possible on the basis of inhibin levels. Between these groups, the distinction was better achieved by the FSH levels (sensitivity of 85%). We conclude that inhibin B levels are a serum marker of Sertoli cell function, but the prediction of the quality of spermatogenesis is not superior to that of FSH levels.

In 1974 Miklos reviewed evidence suggesting an association between sex chromosome pairing failure and spermatogenic arrest. He proposed that distributed over all the chromosomes there are 'meiotic pairing sites' which must be 'saturated' by homologous pairing during pachytene. In unpaired regions these sites are 'activated', and set in motion a process which leads ultimately to the death of the cell. In the present 'extended abstract' we summarize studies we have carried out on XSxraO male mice, that substantiate the main tenets of Miklos' model. Miklos' model is then used as a basis for explaining data we have collected on a large series of XYY male mice.

Introduction. The etiology of male infertility characterized by non-obstructive azoospermia is largely unknown, especially at the molecular level. Identifying dysregulated microRNAs (miRNAs) in male infertility would be useful to achieve a more profound understanding of its pathogenesis. Methods. Small RNA sequencing was performed on the testicular tissues of 10 nonobstructive azoospermic patients with the Sertoli cell only syndrome (SCOS) and 8 obstructive azoospermic individuals with normal spermatogenesis. The expressions of two dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, confirming the results obtained by sequencing analysis. Bioinformatic analysis was undertaken to identify the main pathways impaired in complete spermatogenic failure. Results. A total of 136 miRNAs were detected to be differentially expressed in the Sertoli cell only syndrome group in comparison with the obstructive azoospermia group. Bioinformatic analysis suggested that the altered miRNAs were substantially involved in pathways related to spermatogenesis. Conclusions. Our study investigates the entire profile of miRNAs with emphasis on the crucial role of miRNAs in idiopathic Sertoli cell only syndrome, suggesting potential targets for employing molecular therapeutic strategies in the treatment of spermatogenic failure. [ABSTRACT FROM AUTHOR]

Identifying causal genes of spermatogenic failure on the male‐specific region of Y chromosome (MSY) has been a challenging process. Due to the nonrecombining nature of MSY, haplotype‐based approaches have recently been shown to be promising in identifying associated MSY haplogroups. We conducted an MSY analysis of nonobstructive azoospermia (NOA) patients in a case–control setting (N = 278 and 105 respectively) to identify modal haplogroups strongly associated with NOA. Patients with AZF deletions (AZF+) and no AZF deletions (AZF‐) were compared with the control group. Given the larger sample set of AZF‐ NOA patients, we further investigated the association based on histopathological severity, namely Sertoli cell‐only syndrome and maturation arrest subtypes. We observed no significant enrichment of MSY haplogroups in AZF‐ azoospermic patients (or its subtypes). However, we observed a strongly significant association between haplogroup J2a* and AZF+ patients (FDR‐corrected p =.0056; OR = 7.02, 95%CI 1.89 to 39.20), a haplogroup which also showed significant enrichment for AZFa/b deletions (p = 4x10‐4). We conclude that unlike AZF+ patients, AZF‐ NOA are less likely to have an MSY causative factor with large effect size, thus indicating that the aetiology of AZF‐ NOA, and to some extent AZFc NOA, is more likely to be based on non‐MSY factors. [ABSTRACT FROM AUTHOR]

Background. LR family pyrin domain-containing 14 (NLRP14 or NALP14) is one of the important members of the NLR family and was mainly expressed in testis. It is reported that deficiency in the NALP14 gene in mice can cause spermatogenic failure, and several NALP14 mutations have been found in oligospermia and infertile men. Case Presentation. This study reported two novel NALP14 mutations (c.2076delC: p.L697X and c.T2963C: p.F988S) in our patients with azoospermia. The exonic deletion mutation (c.2076delC) and one missense mutation (c.T2963C) were firstly screened out by whole-exome sequencing (WES) and further verified by amplifying and sequencing the specific exons 5 and 10. Histological analysis of testicular biopsy revealed that NALP14 expression was detected strongly in spermatogonia and weakly in early spermatocytes. Additionally, mutations in this gene caused meiotic arrest, and no postmeiotic round spermatids and mature spermatozoa were observed in the seminiferous tubules. Conclusions. This study and previous literatures showed that NLRP14 mutations are closely related to male infertility; we discovered two novel NALP14 mutations and summarized the kinds of literatures on NLRP14 mutations and male infertility. This is the first report that deletion mutation (c.2076delC) and one missense mutation (c.T2963C) in NALP14 all lead to azoospermia, which is still significant to the clinical auxiliary diagnosis of male infertility. [ABSTRACT FROM AUTHOR]

Busulfan‐induced testicular injury mouse models are commonly used for experiments on spermatogonial stem cell transplantation, treatments for azoospermia due to spermatogenic failure and preserving male fertility after chemotherapy. Here, we investigated the value of testicular quantitative ultrasound for evaluating spermatogenic function in this model. In this study, testicular ultrasound was performed on mice from day 0 to 126 after busulfan treatment (n = 48), and quantitative data, including the testicular volume, mean pixel intensity and pixel uniformity, were analysed. The results revealed that from day 0 to 36, the testicular volume was positively associated with the testicle‐to‐body weight ratio (r =.92). On day 63, the pixel uniformity, which remained stable from day 0 to 36, declined significantly compared with that on day 36 (p <.01). On day 126, when the whole progression of spermatogenesis could be observed in most tubules, the mean pixel intensity also returned to normal (p >.05). In conclusion, testicular quantitative ultrasound could be used as a noninvasive and accurate monitoring method for evaluating spermatogenic function in busulfan‐induced testicular injury mouse models. [ABSTRACT FROM AUTHOR]

Sox8, encoding a SRY‐related HMG box transcription factor, is essential in Sertoli cells for germ cell differentiation via regulation of integrity of the blood–testis barrier (BTB) as well as Sertoli‐germ cell adhesion. Inactivation of Sox8 gene in mice causes postnatal progressive spermatogenic failure, resulting in male infertility. This study aims to investigate whether variants of SOX8 contribute to pathogenesis of idiopathic non‐obstructive azoospermia (NOA) or oligozoospermia. A case–control genetic study was conducted in which all exons and exon–intron boundaries of SOX8 gene were screened in 190 NOA and 139 oligozoospermia cases by Sanger sequencing. The detected variants were examined in 284 normospermic controls. Nine known single‐nucleotide polymorphisms (SNPs) of SOX8 gene were identified, and four of them exist simultaneously in oligo/azoospermia patients. A comparison of allele/genotype frequencies of these variants showed no significant difference between oligo/azoospermia cases and controls. The results indicate that deleterious variants in SOX8 gene may not be a common cause for oligo/azoospermia in Chinese men. Considering ethnic diversity, SOX8 could not be ruled out as a candidate gene for male infertility. The role of SOX8‐mediated Sertoli cell function and BTB integrity played in the pathogenesis of male infertility needs to be further explored in other populations. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of 24 functionally important single nucleotide polymorphisms (SNPs) with male infertility. In this cross-sectional study, we genotyped 24 functionally important single nucleotide polymorphisms in 24 infertility candidate genes in 500 oligo-/astheno-/oligoastheno-/normo-zoospermic infertile men with idiopathic infertility. Sequenom iPlex gold assay was used for genotyping. Sperm count and motility were compared between prevalent genotypes at each test locus. We did not observe any significant difference in the average sperm count between the alternate genotypes for the loci in the KLK3, LRRC6, MEIG1, HSF2, ESR2 and PTIP genes. However, we observed a significant difference in sperm motility between the alternate genotypes for the loci in the LRRC6, MEIG1, HSF2 and PTIP genes. Polymorphisms in the LRRC6 (rs200321595), MEIG1 (rs150031795), HSF2 (rs143986686) and PTIP (rs61752013) genes show association with sperm motility., (© 2022 Wiley-VCH GmbH.)

In this study, a short stature male with infertility is reported. Semen analysis and serum concentrations of FSH, LH, T and PRL were estimated. Chromosome analysis was performed on lymphocytes obtained from both the male and his parents. Cytogenomic studies were performed by fluorescent in situ hybridisation and the Cyto Scan™ HD array analysis to detect Y chromosomal rearrangements and copy number mutations. Semen analysis showed severe oligozoospermia. Numerous spermatogenic cells were observed in the semen, and approximately 60% of the cells examined in semen were primary spermatocytes, showing spermatogenic arrest at the primary spermatocyte level. Cytogenomic studies of blood revealed his karyotype which was 46, X,i( Y) (p11.32) ( Yqter→ Yp11.32:: Yp11.32→ Yqter).ish ( DYZ3++, SRY++, SHOX-). array ( PLCXD1→ SHOX) ×1,( SRY → GOLGA2 P3 Y)×2, ( DHRSX→ ASMT, SPRY3 → IL9 R)×3. The rearrangement Y chromosome is de novo. This is the first case reported with a nonmosaic 46, X, i ( Y) (p11.32), which will be useful to estimate the infertility phenotype-molecular karyotype correlation. Haploinsufficiency of short stature homeobox-containing gene is primarily responsible for the short stature. Aberrations in pseudoautosomal region 1 on the rearranged Y chromosome may result in the deficiency of X- Y pairing or recombination, ultimately lead to the spermatogenic failure. [ABSTRACT FROM AUTHOR]

We aimed to investigate the impact of various varicocelectomy techniques and/or L-carnitine as an adjunct treatment, following the emergence of oxidative stress, on the expression levels of SCF/ c-kit signalling pathways in spermatogenesis. Forty-two rats were divided into seven groups: group 1 (G1) control; group 2 (G2) sham; group 3 (G3) varicocele; group 4 (G4) varicocele + varicocelectomy with testicular nonartery sparing; group 5 (G5) same as G4 but with artery sparing; group 6 (G6) same as G4 but with L-carnitine and group 7 (G7) same as G5 with L-carnitine. m RNA expression levels of SCF and c-kit were measured quantitatively using real-time polymerase chain reaction. CASP-3 activity at protein level was determined, and histological evaluation was performed. m RNA expression level of SCF increased in G6 as compared to control group (3.52-folds change; P = 0.035), whereas m RNA expression level of c-kit gene remained the same. We found that in the left testis of G6 group, m RNA expression level of SCF increased 2.2-folds in comparison with the right testis ( P < 0.05). There were no statistically significant differences in the CASP-3 protein expression levels between the control and other groups. When Cosentino Score analyses of immunostaining were conducted, we observed no significant differences among groups. Spermatogenic failure could be primarily due to a sertoli cell dysfunction. Although surgical treatment has been the best option for management of varicocele, auxiliary agents like L-carnitine may be considered as supportive treatment regimes in addition to conventional surgical treatments. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation has been clearly defined in congenital absence of the vas deferens (CAVD), which is an important cause of obstructive azoospermia. However, the association between oligoasthenospermia and CFTR gene mutation remains controversial. To confirm this issue, 151 infertile Chinese men were screened for CFTR mutation by NGS approach, including 18 CAVD patients, 72 patients with severe oligoasthenospermia and 61 controls with normal sperm parameters. Frequency of mutation in exons of CFTR gene were 66.7% in CAVD patients (12/18) (p < 0.001) and 8.33% in severe oligoasthenospermic patients (6/72) (p < 0.05), both of which were significantly more frequent than that in the controls (0/61). In terms of introns mutation of CFTR gene, there was no significant difference in frequency of 5T between oligoasthenospermic men (5/144, 3.47%) and the controls (4/122, 3.28%) (p = 0.645). In addition, 6 novel mutations in exons of CFTR gene in this study (c.3736A>G, c.635T>G, c.482delA, c.1858C>T, c.2042A>T, c.1586A>C) have not been reported in the Cystic Fibrosis Mutation Database before. Thus, our study provides evidence that CFTR gene mutation may be the aetiology of severe oligoasthenospermia other than CAVD. It may be necessary to screen for CFTR mutations in men with severe oligoasthenospermia before receiving assisted reproductive technology., (© 2021 Wiley-VCH GmbH.)

Infertility is a multiplex disorder in the reproductive system, and men are responsible for more than half of the cases. Nowadays, semen analysis has been considered the critical assessment test to diagnose infertile men; however, it has limitations so that the cause behind infertility in 40% of infertile men is unrevealed. Weaknesses of semen assessment indicate a global need for novel and better diagnostic tools and biomarkers. MicroRNAs are short (about 18-22 nucleotide length) non-coding RNAs that control most (>60%) of our protein-coding genes post-transcriptionally. These molecules are aberrant in the body fluids, and abnormal alterations in their expression level can signify a specific disease such as infertility. Therefore, microRNAs can be novel candidate biomarkers that can diagnose different types of male infertility, including azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. This narrative review aimed to collect and sum up new papers published about the significant role of microRNAs in different male infertility categories., (© 2021 Wiley-VCH GmbH.)

Copy number variations (CNVs), including deletions and duplications on the Y chromosome, are known genetic factors in azoospermia. Therefore, it is important to identify novel pathogenic CNVs related to azoospermia. In this study, we compared CNVs detected by STS-PCR and NGS in 107 individuals with nonobstructive azoospermia (NOA). STS-PCR analysis revealed that 8.14% (9/107) of patients had AZF deletions. The highest percentage of deletions was located in the AZFc region, followed by AZFa and AZFb+c. Positive CNVs, including four duplications, six deletions and three complex CNVs, were detected using NGS methods in 12.15% (13/107) of NOA patients. Both the duplications and deletions detected in q11.223 were confirmed to increase the genetic risk for NOA. A comparison between the STS-PCR results and NGS methods revealed concordant CNV-positive results in 4 of 107 cases (3.74%). The discrepancies included 6 cases with CNVs identified by NGS but not detected by STS-PCR, and two cases were detected by STS-PCR but not by NGS. Notably, four duplications were not identified and three complex CNVs were detected as simple deletions using STS-PCR analysis. The NGS method provides comprehensive results in detecting Y chromosome-linked CNVs, including deletions and duplications, which might broaden our understanding of NOA., (© 2021 Wiley-VCH GmbH.)

Summary: NR5A1 or steroidogenic factor 1 (SF1) is an autosomal gene, which encodes a protein that is a member of nuclear receptor family. NR5A1 regulates the transcription of numerous genes that are expressed in hypothalamic–pituitary–gonadal axis and adrenal cortex which in turn, coordinate the gonadal development, steroidogenesis and sex differentiation. Several mutations in NR5A1 have been reported to cause gonadal dysgenesis with adrenal insufficiency in individuals with 46,XY karyotype. However, studies in the past few years have shown that NR5A1 mutations can also contribute to primary ovarian insufficiency and impaired spermatogenesis. As there is no genetic study on NR5A1 in Indian infertile men, we have sequenced the entire coding region (exons 2–7) of NR5A1 in 502 infertile men of which, 414 were non‐obstructive azoospermic and 88 severe oligozoospermic, along with 427 ethnically matched fertile controls. Interestingly, none of the mutations reported to be associated with male infertility were found in our study, except one polymorphism, rs1110061. However, it was not significantly different between infertile and fertile groups (p = .76). In addition, we have identified six intronic variants; but none of them was significantly associated with male infertility. [ABSTRACT FROM AUTHOR]

Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y-chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies., (© 2020 Blackwell Verlag GmbH.)

Introduction. To investigate the predictive factors for successful repeat microdissection testicular sperm extraction attempts in patients with Klinefelter syndrome. Methods. A total of 28 azoospermic men with nonmosaic Klinefelter syndrome who have received microdissection testicular sperm extraction twice with successful initial microdissection testicular sperm extraction attempts in our institute were studied. Outcome variables (age, serum follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol) of azoospermic men with nonmosaic Klinefelter syndrome and a successful 2nd surgical sperm retrieval attempt (group A) were compared to those with an unsuccessful 2nd sperm retrieval attempt (group B). Results. Twenty-one patients (75%) had successful sperm recovery at the 2nd microdissection testicular sperm extraction attempt. The mean testosterone level at baseline and before the 1st microdissection testicular sperm extraction attempt was higher in group A than in group B (2.7 vs. 0.9 ng/mL, p < 0.01 , and 3.9 vs. 1.1 ng/mL, p = 0.02). Receiver operating characteristic curve analysis identified the threshold baseline testosterone concentration (1.5 ng/mL) of patients with Klinefelter syndrome in predicting successful 2nd sperm retrieval attempts and revealed positive and negative predictive values of 94.44% and 60%, respectively. Conclusion. Azoospermic men with Klinefelter syndrome presenting with low testosterone levels and successful sperm recovery during the first microdissection testicular sperm extraction procedure are unlikely to retrieve sperm on the 2nd microdissection testicular sperm extraction attempt. Hence, these patients should be properly counseled before sperm retrieval. [ABSTRACT FROM AUTHOR]

Background. Aromatase inhibitors (AIs) can significantly improve semen parameters in infertile men. In this study, we investigated the efficacy of AIs for azoospermia in a Chinese population with AZFc microdeletion. Aims. Patients with AZFc microdeletion who were treated with AIs were analyzed retrospectively by collecting clinical data, including their hormone profile and treatment outcome. Patients were divided into those with sperm in their semen after AI treatment (group A) and those without sperm in their semen after AI treatment (group B). Results. The rate of Y chromosome AZF microdeletions was 9.30% (313/3364) from March 2015 to March 2021, among which patients with complete AZFc microdeletion accounted for 63.2% (198/313), and of the 198 patients with AZFc microdeletion, 69.7% (138/198) showed azoospermia. Forty-six (33.3%) of the azoospermic patients had sperm in their semen after AI administration. Testosterone (T) and testosterone-to-estradiol ratio (T/E2) levels were higher in group A than those in group B after treatment, and the differences were significant (T, P = 0.038 ; T/E2, P = 0.004). Paired t -test demonstrated that the change of T levels before and after treatment was statistically significant (P = 0.003). The increased E2 and T/E2 ratio levels before and after treatment were not statistically significant (P = 0.057 and 0.080), but they were close to the threshold value (P = 0.05). Conclusions. Patients with AZFc microdeletion accounted for the largest proportion of male infertility caused by Y chromosome microdeletions. AIs can promote spermatogenesis in azoospermic patients with AZFc microdeletion, and sperm could be found in the semen of some patients after AI administration. T and T/E2 levels after AI treatment could be used as biomarkers to distinguish azoospermic patients with AZFc microdeletion who responded better to AIs from those who did not respond well. [ABSTRACT FROM AUTHOR]

Male infertility is a common and severe problem affecting 7% of population. The main objective of this study is to identify the chromosomal abnormalities, Y microdeletions in infertile men and also to access the frequency of abnormal sperm count. Based on the sperm count and viability, the infertile men were grouped as Azoospermia, Asthenospermia, Oligospermia and the remaining as Idiopathic infertility. A total of 370 infertile men and 60 normal control men were recruited. Chromosomal abnormalities were identified in 3 men (3/370). The prevalence of Y microdeletions in the infertile group is 8/370 in the Azoospermia factor (AZF) region with four AZFc deletion/duplication, two AZFa deletion, one AZF b & AZFc deletion and one case of total AZF a, AZFb & AZFc deletion. However, only five cases of Y microdeletions were identified by Multiplex PCR but an additional three cases by MLPA (Multiplex ligation-dependent probe amplification). Fluorescence in situ hybridisation also confirmed the deletions. Here, we performed MLPA post-multiplex PCR, and our study revealed good yield of the Y microdeletion identification. The partial duplications which are difficult to be identified can now be easily identified by MLPA, and hence, we recommend MLPA as the choice of investigation compared to multiplex PCR for infertile men., (© 2020 Wiley-VCH GmbH.)

Multiple morphological abnormalities of sperm flagella (MMAF) indicate severe teratozoospermia. The fibrous sheath interacting protein 2 (FSIP2) plays an important role in the normal construction of the flagella. In this study, a novel compound heterozygous mutation site of FSIP2, involving c.272_275delinsAGGTTTTTATA (p.L92Vfster74) and c.16788_16791del (p.E5596fs), was identified using whole-exome sequencing in a 32-year-old male. Electron microscope images revealed thick sperm neck, scattered sperm mitochondria, and short sperm tail. In addition, FSIP2 could not be visualized in sperm cells via immunofluorescence staining. Moreover, we used a protein domain prediction tool to identify a potential FSIP2 functional domain (5901-6774), the corresponding deletion of which was responsible for the MMAF phenotype in the infertile man. Finally, we reviewed the literature on FSIP2 and found that FSIP2 mutations are relatively concentrated, with high-frequency mutation regions in exon 16 and exon 17 accounting for 50% (10/20) and 35% (7/20) of cases, respectively. In conclusion, FISP2 is a common pathogenic gene of MMAF, which may provide a rationale for genetic counseling in the next generation of patients with male infertility. [ABSTRACT FROM AUTHOR]

Herein, we introduced a novel individual sperm freezing device named SpermCD, which consists of a right angular cryopiece (RA‐Cryopiece, or "C") and a grooved petri dish ("D"). SpermCD allows embryologists to transfer sperm and perform ICSI on the same focal plane. Thirty‐five patients underwent single sperm cryopreservation using SpermCD, including four patients with non‐obstructive azoospermia (NOA), 14 patients with virtual azoospermia and 17 patients with cryptozoospermia. One hundred and twenty‐five cryopreserved spermatozoa from nine patients were thawed on the day of the oocyte retrieval and 121 spermatozoa were found, with a sperm recovery rate of 97.1 ± 4.6%. Sixty‐five MII oocytes from their spouse were injected with thawed sperm. Normal fertilization and high‐quality embryo rates were 68.0% ± 33.2% and 24.4% ± 22.2%. Nineteen transplantable embryos were formed after fertilization with frozen sperm, eight of which were transplanted in five couples, resulting in four successful deliveries. SpermCD is a simple and practical individual sperm freezing device. [ABSTRACT FROM AUTHOR]

Tobacco's genotoxic components can cause a wide range of gene defects in spermatozoa such as single‐ or double‐strand DNA breaks, cross‐links, DNA‐adducts, higher frequencies of aneuploidy and chromosomal abnormalities. The aim in this study was to determine the correlation between sperm quality determined by standard parameters, sperm DNA maturity tested by Chromomycin A3 (CMA3) staining, sperm DNA fragmentation tested by TUNEL assay and tobacco smoking in association with the single nucleotides polymorphisms (SNP) of three nuclear protein genes in spermatozoa (H2BFWT, PRM1 and PRM2). In this study, semen samples of 167 male patients were collected and divided into 54 non‐smokers and 113 smokers. The target sequences in the extracted sperm DNA were amplified by PCR followed by Sanger sequencing. The results showed the presence of three variants: rs7885967, rs553509 and rs578953 in H2BFWT gene in the study population. Only one variant rs737008 was detected in PRM1 gene, and three variants were detected in the PRM2 gene: rs2070923, rs1646022 and rs424908. No significant association was observed between the concentration, progressive motility, morphology and the occurrence of H2BFWT, PRM1 and PRM2 SNPs. However, sperm parameters were significantly lower in heavy smokers compared to controls (p < 0.01) (sperm count: 46.00 vs. 78.50 mill/ml, progressive motility: 15.00% vs. 22.00%, and morphology 4.00% vs. 5.00%, respectively). Moreover, the heavy smoker individuals exhibited a considerable increase in CMA3 positivity and sDF compared to non‐smokers (p < 0.01) (29.50% vs. 20.50% and 24.50% vs. 12.00%, respectively). In conclusion, smoking altered sperm parameters and sperm DNA integrity, but did not show a linkage with genetic variants in H2BFWT, and protamine genes (PRM1 and PRM2). [ABSTRACT FROM AUTHOR]

Obesity and male infertility are problems that affect population. Exercise is a nonpharmacological way to reduce the negative health effects of obesity. The purpose of this study was to examine the effects of exercise on hormone levels, blood‐testis barrier, and inflammatory and oxidative biomarkers in rats that became obese due to a high‐fat diet (HFD). Male rats received a standard diet (STD group) or a HFD (HFD group) for 18 weeks. During the final 6 weeks of the experiment, swimming exercises (1 h/5 days/week) were given to half of these animals (STD + EXC and HFD + EXC groups). Finally, blood and testicular tissues were analysed by biochemical and histological methods. Body weight, leptin, malondialdehyde, interleukin‐6, TNF‐alpha and myeloperoxidase levels, apoptotic cells and DNA fragmentation were increased, and testis weight, insulin, FSH, LH, testosterone, glutathione and superoxide dysmutase levels, proliferative cells, ZO‐1, occludin, and gap junction protein Cx43 immunoreactivity were decreased in the HFD group. All these hormonal, morphological, oxidative and inflammatory biomarkers were enhanced in the HFD + EXC group. It is thought that exercise protected testicular cytotoxicity by regulating hormonal and oxidant/antioxidant balances and testicular function, inhibiting inflammation and apoptosis, as well as preserving blood‐testis barrier. [ABSTRACT FROM AUTHOR]

Gene expression in meiotic cells in the testis is characterized by intense transcriptional activity and alternative splicing. These processes are mainly controlled by RNA‐binding proteins expressed strongly in germ cells. Functional impairments in any of these proteins' functions can lead to defects in meiosis and thus severe male infertility. Here, we have identified a homozygous frameshift mutation (NM_014469.4:c.301dup; p.Ser101LysfsTer29) in the RNA‐binding motif protein, X‐linked like 2 (RBMXL2) gene in a man with an azoospermia due to meiotic arrest. As RBMXL2 is known to be crucial for safeguarding the meiotic transcriptome in mice testes, we hypothesized that this variant leads to cryptic splice site poisoning. To determine the variant's impact on spermatogenesis, we confirmed the absence of RBMXL2 protein in the patient's testis tissue and then evidenced abnormal expression of several spermatogenesis proteins (e.g. meiosis‐specific with coiled‐coil domain) known to be altered in rbmxl2 knock‐out mice with meiotic arrest. Our results indicate that RBMXL2's function in spermatogenesis is conserved in mammals. We hypothesize that deleterious variant in the RBMXL2 gene can result in male infertility and complete meiotic arrest, due to the disruption of gene expression by cryptic splice site poisoning. [ABSTRACT FROM AUTHOR]

Spermatogenesis is regulated by complex tissue specific gene expression in the testis to achieve normal male fertility. X‐chromosome specific TATA binding protein (TBP)‐associated factor 7L (hTAF7L) is one of the transcriptional regulator genes considered essential for spermatogenesis. The aim of this study was to evaluate the role of variants/mutations in the testis‐specific hTAF7L gene in non‐obstructive azoospermia and severe oligozoospermia male infertility. We studied 156 idiopathic non‐obstructive azoospermic, severe oligozoospermic infertile males and 50 fertile proven controls. Infertile males and control subjects were genotyped for variants of the hTAF7L gene using polymerase chain reaction and a direct Sanger sequencing approach. The odds ratio evaluated the association of hTAF7L gene variants with idiopathic male infertility. The variants found in the hTAF7L gene were subjected to an in‐silico analysis study. In infertile study subjects, we observed 11 single base pair nucleotide changes at various exons and three frameshift variants at exon 10 in the hTAF7L gene. We also found more than one variant in some non‐obstructive azoospermia and severe oligozoospermia infertile males along with control subjects. All these variants changed the amino acid sequences in the hTAF7L gene. However, similar changes were also seen in fertile subjects, and the differences were not statistically significant. In‐silico tools also predicted that the variants were likely to be benign. The variants in cDNA of the hTAF7L gene were typical SNPs. It is found that the hTAF7L gene is highly polymorphic and these missense variants are not directly associated with male infertility. However, we feel that more studies are needed to elucidate the role of multiple variants of the hTAF7L gene in the process of normal spermatogenesis. [ABSTRACT FROM AUTHOR]

Spermatogenesis associated 16 (SPATA16) gene plays an important role in acrosome formation. In this study, we analysed SPATA16 promoter methylation in 29 oligozoospermic infertile and 16 normozoospermic fertile sperm samples and in testicular biopsy from 16 non‐obstructive azoospermic and 2 obstructive azoospermic individuals. Next, we analysed SPATA16 level in sperm from 8 oligozoospermic infertile, 6 normozoospermic fertile, 9 IVF failed normozoospermic and 10 IVF successful normozoospermic samples by immunoblotting. This was followed by the analysis of SPATA16 expression in testicular biopsy from azoospermic individuals (n = 8) in comparison to normozoospermic individuals (n = 2). Oligozoospermic infertile sperm samples showed significantly higher methylation in the SPATA16 promoter region. Similarly, testicular biopsy from azoospermic men also showed significantly higher level of DNA methylation. Sub‐group analysis of infertile sperm and testicular biopsy samples showed a direct correlation between DNA methylation and the degree of spermatogenic impairment. Oligozoospermic infertile samples and IVF failed samples showed reduced SPATA16 expression in comparison to normozoospermic fertile and IVF successful samples, respectively. Human biopsy analysis showed a significant decrease in SPATA16 expression in hypospermatogenesis, maturation arrest and Sertoli cell only syndrome. In conclusion, hypermethylation in SPATA16 promoter shows a highly significant correlation with infertility, which is consistent with its down‐regulation in infertility. [ABSTRACT FROM AUTHOR]

To investigate the serum levels of reproductive hormones in men with azoospermia and explore the correlation between abnormal reproductive hormones and the results of testicular biopsy and seminiferous extraction. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and pituitary prolactin (PRL), were measured by Radio immunoassay. Testicular biopsy was used to determine whether patient's had spermatozoa. Spearman's correlation analysis was used to analyse the correlation between LH, FSH, testicular volume, and spermatogenic function. Receiver operator characteristic (ROC) curves were used to evaluate the efficacy and significance of LH and FSH for the detection of spermatozoa and copy number variation sequencing (CNV‐seq). Compared with the control group, the serum levels of FSH and LH in the azoospermia group were significantly up‐regulated (p < 0.001). Prolactin (PRL) and testosterone levels did not differ significantly between the two groups (p > 0.05). The serum levels of FSH and LH were negatively correlated with testicular spermatogenic function and testicular volume. The areas under the ROC curves for determining FSH and LH potency by testicular biopsy with or without spermatozoa were 0.640 and 0.622, respectively. The areas under the ROC curves for the potency of FSH and LH, as judged by CNV detection results, were 0.523 and 0.534, respectively. Serum levels of FSH and LH are associated with azoospermia and may be of predictive significance in the clinical setting for the acquisition of spermatozoa by testicular biopsy. [ABSTRACT FROM AUTHOR]

Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin‐3‐Ο‐glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 μM and 100 μM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 μM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low‐concentration C3G supplementation (50 μM) was negatively correlated with sperm ROS levels (r = −0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Testicular sperm retrieval (TSR) techniques are valuable in the context of severe idiopathic male factor infertility; however, there are few studies in the literature examining the long‐term impact of TSR on testicular function. The objective was to determine whether testicular sperm aspiration (TESA) or microdissection testicular sperm extraction (micro‐TESE) worsens the pre‐existing spermatogenesis deficiency in men with either cryptozoospermia or severe oligozoospermia. The study population consisted of 145 men with either cryptozoospermia or severe oligozoospermia that underwent TESA or micro‐TESE and had long‐term post‐operative semen analyses (SA). Patients with SA prior to and following TSR were included (n = 24). Amongst them, 16 men underwent TESA and 8 underwent micro‐TESE. The follow‐up SA was obtained at a mean of 3.0 ± 2.0 years following TSR (range: 0.3–8.3 years) amongst all participants. The post‐operative semen parameters in the TESA group were similar to the pre‐intervention parameters (p > 0.1). Similarly, the micro‐TESE cohort did not demonstrate significant alterations in semen parameters post‐intervention (p > 0.05). None of the men in the study became azoospermic following the TSR. Our study indicates TESA or micro‐TESE do not appear to worsen the pre‐existing spermatogenesis deficiencies in cryptozoospermic and oligozoospermic men over a long‐term period. Larger studies are required to corroborate these findings. [ABSTRACT FROM AUTHOR]

Genetic variants affecting the interaction of FSH–FSHR may negatively affect the male reproductive potential. The aim of this case–control study was to evaluate FSHB c.–211G>T and FSHR c.2039A>G variants in a cohort of infertile men from Central Black Sea Region in Turkey. One hundred and nine infertile men and 50 proven fertile controls were enrolled in the study. Genotyping was assessed by RFLP. The genotype frequencies of FSHB –211G>T and FSHR 2039A>G showed significant variation between infertile and fertile groups (χ2, p = 0.046, GG vs. GT+TT, and p = 0.008, AA vs. AG+GG). FSHB –211GG was found to be higher in patients with OAT compared to fertile controls (82.3% vs. 64.0%, χ2, p = 0.028). The distribution of FSHR 2039A>G alleles was different between infertile and fertile men (χ2, p = 0.005, total infertile vs. fertile groups, p = 0.019, OAT vs. NOA vs. fertile groups). Further analysis showed that the frequencies of FSHR 2039AA wild‐type genotype were higher in the oligoasthenoteratozoospermic and non‐obstructive azoospermic groups compared with the controls (χ2, 39.3% vs. 17.0%, p = 0.012, and 37.5% vs. 17.0%, p = 0.025 respectively). Our results showed wild‐types of FSHB –211G>T and FSHR 2039A>G variants may cause susceptibility to male infertility in the Central Black Sea Region of Turkey. [ABSTRACT FROM AUTHOR]

This study was carried out to evaluate the effectiveness of cryopreservation of human spermatozoa by freezing testicular seminiferous tubule with a new cryocarrier named 'novel cryopiece'. Testicular tissue (TT) was collected from patients who underwent diagnostic testicular biopsy. Overall, 35 TT samples were obtained. Each TT sample was equally divided into four groups named (e.g. G1, G2, G3 and Gc). G1 was frozen as testicular seminiferous tubule using novel cryopiece, G2 was frozen as testicular cell suspensions using novel cryopiece, G3 was frozen as testicular cell suspensions using 0.25 ml straw, and Gc was not frozen. The samples in G1 and G2 experimental groups were cryopreserved in five separate aliquots and stored in the same cryovial. The freeze–thaw sperm DNA fragmentation index (DFI) of G2 was lower than that of G3 (20.27 ± 5.40 vs 23.55 ± 6.02; p = 0.004). After thawing, spermatozoa could be found in all 35 testicular seminiferous tubule specimens in G1; however, it could not be found in 2 of 35 (5.7%) and 1 of 35 (2.9%) testicular cell suspensions samples in G2 and G3 respectively. This study indicates that novel cryopiece presented for the cryopreservation of testicular seminiferous tubules and testicular cell suspension is simple and effective. [ABSTRACT FROM AUTHOR]

We characterised and correlated the histological and hormonal aspects of a cohort of 261 azo/oligozoospermic men, applying a quantitative/qualitative evaluation of testicular tissue and serum and intratesticular hormonal measurements. One hundred and 93 azo⁄oligozoospermic patients were diagnosed as: complete sertoli cell only syndrome ( cSCOS), n = 76; focal SCOS, n = 31; maturation arrest, n = 34; hypospermatogenesis, n = 17; mixed atrophy, n = 25; and severe atrophy, n = 10. Normal spermatogenesis was observed in 68 infertile men (controls). Patients with cSCOS, focal SCOS, mixed and severe atrophy had larger LC/clusters (11.5; 11.0; 10.7; 18.9 LC/cluster) than controls (6 LC/cluster; P < 0.001). cSCOS, focal SCOS, mixed and severe atrophy patients had higher FSH, LH and lower T/LH ratio serum levels than the other groups. Intratesticular testosterone concentrations were higher in tissues with complete or focal SCOS (45.6 ng mg−1 protein) and mixed atrophy (79.0 ng mg−1 protein) than normal tissues (20.3 ng mg−1 protein; P = 0.03 and P = 0.007). Considering all subjects, significant correlations were found between T/LH ratio and Leydig cells/cluster ( r = 0.510, P < 0.001), FSH levels ( r = −0.692, P < 0.001) and with intratesticular testosterone ( r = −0.354, P = 0.001); these correlations follow the pattern of severity of spermatogenic damage. By a thorough histological evaluation, we validate the concept that the severity of spermatogenic impairment is associated with major morphological and functional disturbance of the Leydig cell compartment. [ABSTRACT FROM AUTHOR]

Results of numerous studies gave contradictory conclusions when analysing associations between copy number variants (CNVs) within the azoospermia factor (AZF) locus of the Y chromosome and idiopathic male infertility. The aim of this study was to identify the presence and possible association of CNVs in the AZF region of Y chromosome with idiopathic male infertility in the Serbian population. Using the multiplex ligation‐dependent probe amplification technique, we were able to detect CNVs in 24 of 105 (22.86%) infertile men and in 11 of 112 (9.82%) fertile controls. The results of Fisher's exact test showed a statistically significant difference between cases and controls after merging g(reen)–r(ed)/g(reen)–r(ed) and b(lue)2/b(lue)3 partial deletions identified in the AZFc region (p = 0.024). At the same time, we observed a trend towards statistical significance for a deletion among gr/gr amplicons (p = 0.053). In addition to these, we identified a novel complex CNV involving inversion of r2/r3 amplicons, followed by b2/b3 duplication and b3/b4 deletion, respectively. Additional analyses on a larger study group would be necessary to draw meaningful conclusions about associations among CNVs that presented with higher frequency in the infertile men than the fertile controls. [ABSTRACT FROM AUTHOR]

Reciprocal translocation and Robertsonian translocation are known to be causative factors of male infertility. However, the association between autosomal reciprocal translocation, Robertsonian translocation and semen parameters remains controversial. We performed a retrospective study and systematic review to investigate semen parameters in patients with autosomal reciprocal translocation or Robertsonian translocation. We recruited a total of 1,033 controls, 723 reciprocal translocation carriers and 326 Robertsonian translocation carriers. Men in the control, reciprocal translocation and Robertsonian translocation groups had a median age of 32.0 (95% CI, 32.0–33.0), 32.0 (95% CI, 32.0–33.0) and 33.0 (95% CI, 32.0–33.0) years respectively. Results showed that sperm concentration, total number per ejaculate, total motility, progressive motility of autosomal reciprocal translocation and Robertsonian translocation carriers were statistically lower than controls (p <.001). Eleven studies featuring 794 patients were enrolled in this systematic review. Compared with controls, autosomal reciprocal translocation and Robertsonian translocation carriers showed lower sperm concentration, total motility, progressive motility and normal morphology. Our results support the conclusion that sperm concentration, total number per ejaculate, total motility and progressive motility are significantly lower in autosomal reciprocal translocation and Robertsonian translocation carriers than in controls. [ABSTRACT FROM AUTHOR]

Classic therapies are usually ineffective in the treatment of patients with very poor sperm density. The aim of this study was to determine the effect of acupuncture on these males. Semen samples of 20 patients with a history of azoospermia were examined by light microscope (LM) and scanning electron microscope (SEM), with which a microsearch for spermatozoa was carried out. These examinations were performed before and 1 month after acupuncture treatment and revealed that the study group originally contained three severely oligoteratoasthenozoospermic (OTA), two pseudoazoospermic and 15 azoospermic patients. The control group was comprised of 20 untreated males who underwent two semen examinations within a period of 2–4 months and had initial andrological profiles similar to those of the experimental group. No changes in any of the parameters examined were observed in the control group. There was a marked but not significant improvement in the sperm counts of severely OTA males following acupuncture treatment (average=0.7±1.1×106 spermatozoa per ejaculate before treatment vs. 4.3±3.2×106 spermatozoa per ejaculate after treatment). A definite increase in sperm count was detected in the ejaculates of 10 (67%) of the 15 azoospermic patients. Seven of these males exhibited post-treatment spermatozoa that were detected even by LM. The sperm production of these seven males increased significantly, from 0 to an average of 1.5±2.4×106 spermatozoa per ejaculate (Z=-2.8, P≤0.01). Males with genital tract inflammation exhibited the most remarkable improvement in sperm density (on average from 0.3±0.6×106 spermatozoa per ejaculate to 3.3±3.2×106 spermatozoa per ejaculate; Z=-2.4, P≤0.02). Two pregnancies were achieved by the IVF-ICSI procedure. It is concluded that acupuncture may be a useful, nontraumatic treatment for males with very poor sperm... [ABSTRACT FROM AUTHOR]

In this study, we estimated the protective role of Moringa oleifera leaf ethanolic extract (MOLE) against obesity‐associated testicular dysfunction. Fifty male albino rats were randomly assigned to five groups (n = 10): Group I (basal diet), group II (basal diet plus MOLE orally), group III (high‐fat diet—HFD), group IV (HFD plus oral MOLE) and group V (HFD for 8 weeks followed by a basal diet plus oral MOLE for 6 weeks). The study duration extended for 14 weeks. Serum collected to investigate testosterone, FSH and LH levels. Testicular tissues were used to determine levels of SOD, glutathione, catalase and malondialdehyde. Semen was collected to estimate its quality (morphology, motility and concentration). Morphological changes in the testis were investigated by histopathological and immunohistochemical techniques. Compared with both control treatment and MOLE treatment, serum testosterone, FSH, LH, testicular enzymatic catalase, SOD, GSH, survivin immunoreactivity, sperm quality and testicular weight were all significantly decreased in rats treated with HFD, while there were significant increases in testicular malondialdehyde and caspase‐3 immunoreactivity. MOLE improved all harmful effects of HFD. Improvements were more pronounced in the protected (G 4) than the treated (G 5) group. MOLE could be a potential solution for obesity‐associated fertility problem. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a disorder of structure and function of motor ciliary and dyskinetic activity of ciliary in the fallopian tubes of affected women and could lead to infertility in some cases. In vitro fertilisation (IVF) is a choice of treatment in infertile women with PCD, which could conquer the tubal dysfunction. In this case study, we report a PCD affected woman with infertility who was treated by IVF and pregnancy was achieved but it failed due to the spontaneous abortion. We also performed whole‐exome sequencing for this case and her PCD‐affected sister, which did not reveal any genetic abnormality related to the PCD or infertility. [ABSTRACT FROM AUTHOR]

Although a wide array of interventions exist for men seeking fertility after vasectomy, up to 6% of them will elect for a vasectomy reversal. While the widespread adoption of telemedicine promises convenience and improved access, lack of ability to do a physical examination may hinder appropriate counselling. Although vasectomy reversal is successfully completed in most of the men either with a vasovasostomy or a vasoepididymostomy, there could be various reasons for the inability to successfully complete the operation. Our commentary outlines the reasons why a vasectomy reversal is not possible or successful. We also discuss a pre‐operative management algorithm in men seeking vasectomy reversal to ensure appropriate counselling with a thorough pre‐operative history, physical examination and on occasion, hormonal evaluation. [ABSTRACT FROM AUTHOR]

There are a number of risk factors, especially viral diseases, which can lead to infertility. Among the various viral infections, much attention has been given to the role of the Papillomaviridae and Herpesviridae. After collecting 82 semen samples (37 teratospermia, 2 asthenozoospermia, 2 oligoasthenospermia, 1 oligospermia, 6 asthenoteratospermia and 34 normal semen samples), and washing them, the DNA from both freshly ejaculated spermatozoon and washed spermatozoa was extracted. Subsequently, the prevalence of EBV, CMV, HSV‐1, HSV‐2, VZV and HPV was evaluated using Multiplex PCR and Nested PCR. In this study, 1 normal and 5 abnormal semen samples were infected with HSV‐1 (1 normal, 4 teratospermia and 1 oligoasthenospermia). In addition, there were 2 VZV‐positive samples (both were teratozoospermia). Nested PCR indicated that 1 asthenozoospermia, 1 asthenoteratospermia, 3 teratospermia and 4 normal samples were HPV positive (including 8 HPV‐18 and 1 HPV‐33). Among 9 HPV‐positive subjects, 3 samples were negative after washing the infected samples. The prevalence of EBV, CMV, VZV, HSV‐1 and HSV‐2 remained unchanged prior to and after washing. Maybe sperm washing can be useful to eliminate HPV infection from semen samples, but further investigation is required because of the small number of samples. [ABSTRACT FROM AUTHOR]

The fungicide iprodione (IPR) and the insecticide chlorpyrifos (CPF) are concurrently applied for early disease control in fruits and other crops. However, there are no available data about the impacts of their co‐exposure. Additionally, IPR and CPF are known as endocrine disruptors that can cause reproductive toxicity. The outcomes of their co‐exposure on the development of male reproductive organs are still unknown. Therefore, this study aimed to assess the risk of exposure to these pesticides, particularly on the postnatal development of the male albino rat reproductive system from postnatal days 23–60. The results revealed that a single IPR or CPF exposure has harmful consequences on the reproductive development and function manifested by reduced testicular weight, serious changes in sperm characteristics, reproductive hormone level imbalance, testicular enzymes, oxidative stress and apoptosis‐related enzymes, which correlated with transcription levels of steroidogenic‐ and spermatogenic‐related genes. Histopathologically, both compounds caused severe damage in the testis and accessory glands architecture. Notably, co‐exposure to IPR and CPF in rats caused more serious damage, indicative of an additive effect than individual exposure, so concurrent exposure should be avoided as it is more hazardous, especially on male fertility. [ABSTRACT FROM AUTHOR]

Altered protamine 1 (PRM1)/ protamine 2 (PRM2) mRNA ratio in testicular biopsy samples correlates with sperm quality and its fertilising ability. This study is planned to assess PRM1/ PRM2 mRNA ratio in subgroups of azoospermia to suggest a more reliable and accurate marker for assessing sperm quality in nonobstructive azoospermia (NOA). A cross‐sectional study was done on testicular biopsy samples, taken from 106 azoospermic patients. Samples were histologically classified into subgroups: 36 obstructive azoospermia (OA), and two groups of NOA: 41 round spermatid maturation arrest (SMA) and 29 Sertoli cell‐only syndrome (SCOS). OA samples showed histologically normal spermatogenesis and serve as a positive control. mRNA expression of jumonji domain‐containing 1A (JMJD1A), PRM1, PRM2 and transition nuclear proteins (TNP1, TNP2) genes was determined, by RT‐qPCR. Significantly lower expression of JMJD1A (p <.001), PRM1 (p =.0265) and PRM2 (p =.0032) has been seen in the SCOS group of NOA. We found significant (p <.001) increase in PRM1/PRM2 mRNA ratio in testicular biopsy samples of SCOS group of NOA patients and significant negative correlation of PRM1/PRM2 mRNA ratio with JMJD1A. Hence, PRM1/PRM2 mRNA ratio may represent a more reliable and accurate marker to assess sperm quality in NOA in addition to standard semen parameters. [ABSTRACT FROM AUTHOR]