Protamine Genes Research Articles

Correlation analysis of the PRM1, STK35 and IFT27 level of expression genes with the quality of native and deposited seed of holsting bulls

The research aim is a correlation analysis of the PRM1, STK35 and IFT27 genes mRNA expression with the native and decryoconserved sperm quality indicators of Holstein bulls to search for effective transcriptomic biomarkers of bull semen. In the study course, native and decryoconserved sperm of seven Holstein bulls were used. To solve the study problems, eight indicators of sperm quality were studied, the studied genes in native and decryoconserved spermatozoa expression was analyzed in real time PCR. Nonparametric probabilistic and statistical methods were used, the analysis of rank correlation was carried out using Spearman’s criterion. Higher expression of the studied genes was mainly noted in frozen--thawed sperm compared to native. The mRNA expression level of the protamine gene (PRM1) did not give a reliable correlation with sperm parameters: The level ITF27 gene mRNA expression was significantly positively correlated with the content of defective cells from frozen--thawed sperm (0.714, p=0.05) and dead cells (0.714, p=0.0545) from native sperm. A negative correlation was noted with the content of normal cells in frozen--thawed sperm (-0.750, p=0.038) and live cells (-0.714, p=0.0545) in native sperm. The ITF27 gene transcript (mRNA) showed a negative correlation (-0.703, p=0.0545) in terms of the acrosome defect of frozen--thawed spermatozoa. In terms of the content of reactive oxygen species (ROS), the mRNA of the ITF27 gene had a significant positive correlation (0.786, p=0.0251). The STK35 gene transcript (mRNA) was the only one of all the studied mRNAs that had an average negative correlation with sperm motility in native (-0.692, p=0.052) and frozen--thawed sperm (-0.876, p=0.035). These studies can be used to create a system of non-invasive transcriptional markers of bull sperm quality.

Derepression of Y-linked multicopy protamine-like genes interferes with sperm nuclear compaction in D. melanogaster

Across species, sperm maturation involves the dramatic reconfiguration of chromatin into highly compact nuclei that enhance hydrodynamic ability and ensure paternal genomic integrity. This process is mediated by the replacement of histones by sperm nuclear basic proteins, also referred to as protamines. In humans, a carefully balanced dosage between two known protamine genes is required for optimal fertility. However, it remains unknown how their proper balance is regulated and how defects in balance may lead to compromised fertility. Here, we show that a nucleolar protein, modulo, a homolog of nucleolin, mediates the histone-to-protamine transition during Drosophila spermatogenesis. We find that modulo mutants display nuclear compaction defects during late spermatogenesis due to decreased expression of autosomal protamine genes (including Mst77F) and derepression of Y-linked multicopy Mst77F homologs (Mst77Y), leading to the mutant's known sterility. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear compaction defects, similar to modulo mutant, indicating that Mst77Y is a dominant-negative variant interfering with the process of histone-to-protamine transition. Interestingly, ectopic overexpression of Mst77Y caused decompaction of X-bearing spermatids nuclei more frequently than Y-bearing spermatid nuclei, although this did not greatly affect the sex ratio of offspring. We further show that modulo regulates these protamine genes at the step of transcript polyadenylation. We conclude that the regulation of protamines mediated by modulo, ensuring the expression of functional ones while repressing dominant-negative ones, is critical for male fertility.

Possible Harmful Effects of Smoking Hookah on Sperm DNA Fragmentation Index and Protamine Genes Expression in Normozoospermic Men

In recent years, smoking water pipes or hookah has increased among adolescents in most countries. Although there is evidence in support of the negative effects of this type of smoking on human health, such as the increased risk of lung disease, little is known about the potential effects of hookah smoking on the male reproductive system, especially on the molecular aspects of sperm. This cross-sectional study examined sperm DNA fragmentation index, protamine 1 and 2 (PRM1 and PRM2) genes expression, and oxidant status in normozoospermic hookah smokers in comparison with non-smoker controls. Our results showed significantly higher rates of DNA fragmentation, protamine deficiency, and abnormal chromatin condensation in the spermatozoa of hookah smokers (P < .0001). Also, protamine gene expression showed a remarkable decrease in hookah smokers (1.55 ± 2.54 and 0.33 ± 0.54) compared to the controls (3.49 ± 5.41 and 1.22 ± 1.96), although the reduction was not statistically significant (P = .155 and P = .066, respectively). Moreover, a significantly higher level of semen MDA was observed in the case group compared to the controls (0.39 ± 1.04 vs 0.15 ± 0.21; P = .013). According to our study, although hookah smoking does not have a significant effect on sperm parameters, it may have deleterious effects on DNA integrity, oxidative status, and nuclear protein levels of spermatozoa.

Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility.

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).

H3K36me2 methyltransferase NSD2 orchestrates epigenetic reprogramming during spermatogenesis.

Spermatogenesis is precisely controlled by sophisticated gene expression programs and is driven by epigenetic reprogramming, including histone modification alterations and histone-to-protamine transition. Nuclear receptor binding SET domain protein 2 (Nsd2) is the predominant histone methyltransferase catalyzing H3K36me2 and its role in male germ cell development remains elusive. Here, we report that NSD2 protein is abundant in spermatogenic cells. Conditional loss of Nsd2 in postnatal germ cells impaired fertility owing to apoptosis of spermatocytes and aberrant spermiogenesis. Nsd2 deficiency results in dysregulation of thousands of genes and remarkable reduction of both H3K36me2 and H3K36me3 in spermatogenic cells, with H3K36me2 occupancy correlating positively with expression of germline genes. Nsd2 deficiency leads to H4K16ac elevation in spermatogenic cells, probably through interaction between NSD2 and PSMA8, which regulates acetylated histone degradation. We further reveal that Nsd2 deficiency impairs EP300-induced H4K5/8ac, recognized by BRDT to mediate the eviction of histones. Accordingly, histones are largely retained in Nsd2-deficient spermatozoa. In addition, Nsd2 deficiency enhances expression of protamine genes, leading to increased protamine proteins in Nsd2-deficient spermatozoa. Our findings thus reveal a previously unappreciated role of the Nsd2-dependent chromatin remodeling during spermatogenesis and provide clues to the molecular mechanisms in epigenetic abnormalities impacting male reproductive health.

The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility.

Inherited microorganisms can selfishly manipulate host reproduction to drive through populations. In Drosophila melanogaster, germline expression of the native Wolbachia prophage WO proteins CifA and CifB cause cytoplasmic incompatibility (CI) in which embryos from infected males and uninfected females suffer catastrophic mitotic defects and lethality; however, in infected females, CifA expression rescues the embryonic lethality and thus imparts a fitness advantage to the maternally transmitted Wolbachia. Despite widespread relevance to sex determination, evolution, and vector control, the mechanisms underlying when and how CI impairs male reproduction remain unknown and a topic of debate. Here, we use cytochemical, microscopic, and transgenic assays in D. melanogaster to demonstrate that CifA and CifB proteins of wMel localize to nuclear DNA throughout the process of spermatogenesis. Cif proteins cause abnormal histone retention in elongating spermatids and protamine deficiency in mature sperms that travel to the female reproductive tract with Cif proteins. Notably, protamine gene knockouts enhance wild-type CI. In ovaries, CifA localizes to germ cell nuclei and cytoplasm of early-stage egg chambers; however, Cifs are absent in late-stage oocytes and subsequently in fertilized embryos. Finally, CI and rescue are contingent upon a newly annotated CifA bipartite nuclear localization sequence. Together, our results strongly support the Host modification model of CI in which Cifs initially modify the paternal and maternal gametes to bestow CI-defining embryonic lethality and rescue.

Dynamic Expression and Chromatin Incorporation of ACT and CREM Transcription Factors in Testis Tissues of Infertile Men.

ObjectiveActivator of CREM in the testis (ACT) is a tissue specific transcription factor which activates cAMP responsive element modulator (CREM), a key transcription factor in differentiation of round spermatids into mature spermatozoa. They bind to CRE region in the promoters of transition protein genes (TNP1, TNP2) and protamine genes (PRM1 and PRM2), which are essential for sperm chromatin compaction, and regulates their transcription. This study was conducted to consider the expression of ACT and CREM and their regulatory roles on the expression of PRM1, PRM2, TNP1 and TNP2 genes in testis tissues of infertile men.Materials and MethodsIn this case-control study, testicular biopsies were collected from 40 infertile men and classified into three groups: obstructive azoospermia (OA, n=10, positive control), round spermatid maturation arrest (SMA, n=20), Sertoli cell-only syndrome (SCOS, n=10, negative control group). Using quantitative real-time polymerase chain reaction (PCR), the expression profile of ACT, CREM, TNP1, TNP2, PRM1 and PRM2 genes were assessed in testicular samples and incorporation of ACT and CREM proteins on the promoters of PRM1, PRM2, TNP1 and TNP2 genes were also evaluated by ChIP-real time PCR. ResultsOur results demonstrated significant decrease in the expression levels of ACT, CREM and in their incorporations on their target genes in SMA group in comparison to control groups (P<0.05).ConclusionThese data confirm that there is low expression and incorporation of ACT and CREM and of their target genes in infertilities which are associated with post-meiotic arrest.

Potential effect of tobacco cigarettes smoking on global DNA methylation status and protamines transcripts in human spermatozoa

BackgroundEpigenetics refers to an alteration in gene expression without alteration in the sequence of DNA and this process may be affected by environmental factors and lifestyle like cigarette smoking. This study was designed to evaluate the potential effect of cigarette smoking on the global DNA methylation status and the transcription level of protamine 1 and protamine 2 in human spermatozoa. A total of 188 semen samples were collected from men with a mean age of 34.9 ± 5.8 years old (98 heavy smokers and 90 non-smokers). The DNA and RNA were isolated from purified spermatozoa, then the status of global DNA methylation and the transcription level of protamine 1 and protamine 2 were evaluated using ELISA and qPCR, respectively. The chromatin non-condensation and DNA fragmentation in human spermatozoa were evaluated using chromomycin A3 staining and TUNEL assay, respectively.ResultsA significant increase has been found in the status of global DNA methylation in spermatozoa of heavy smokers compared to non-smokers (7.69 ± 0.69 ng/μl vs. 4.90 ± 0.40 ng/μl, P < 0.001). Additionally, a significant reduction has been found in transcription level of protamine 1 (25.49 ± 0.31 vs. 23.94 ± 0.40, P < 0.001) and protamine 2 (28.27 ± 0.39 vs. 23.45 ± 0.30, P < 0.001) in heavy smokers. A downregulation has been found in the transcription level of protamine 1 and protamine 2 with a fold change of 0.497 and 0.047, respectively. A significant increase has been shown in the level of DNA fragmentation and chromatin non-condensation in heavy smokers compared to non-smokers (P < 0.001). On the other hand, a significant positive correlation has been found between sperm chromatin non-condensation, sperm DNA fragmentation, transcription level of protamine 1, transcription level of protamine 2, and global DNA methylation status (r = 0.304, P < 0.001; r = 0.399, P < 0.001; r = 0.216, P = 0.003; r = 0.494, P < 0.001, respectively).ConclusionTobacco cigarette smoking has a potential influence on the global DNA methylation and the transcription level of protamine genes in human spermatozoa, and consequently, affect negatively on the semen parameters.

Gordon Henry Dixon. 25 March 1930—24 July 2016

Gordon H. Dixon was a highly influential scientist who excelled in all the stages of his career and in each laboratory of every institution at which he was a member. Gordon began his graduate career at the University of Cambridge and completed his studies at the University of Toronto on the subject of transpeptidation reactions in biological systems. At an early stage of his career, he developed the technique of starch gel electrophoresis with Oliver Smithies and made important discoveries on the structure of human haptoglobins. Subsequently, Gordon contributed to the determination of the structure and active sites and mechanisms of action of trypsin and chymotrypsin and made seminal discoveries related to understanding the structure of the protein hormone insulin. However, he is best known for his later studies on the regulation of protamine genes and chromatin transitions in spermatogenesis. He is often considered to be the father of the protamine molecular biology underlying this gene system and his research is continually cited to this day. Gordon contributed to the identification and sequencing of the protamine genes, the discovery that methionine was required for initiation of protamine synthesis, understanding the roles of histone hyperacetylation and protamine phosphorylation, and the generation of the highly compact nucleoprotamine structure present in sperm, primarily using trout as a model system. Gordon is fondly remembered as a brilliant and very generous scientist by all his mentees, representing all levels from undergraduates to PhD and postdoctoral fellows, who provided a scientifically stimulating atmosphere in which they could develop their careers. From a more personal perspective, he also had a fun side and was devoted to his family. Gordon was a person who, owing to his legacy of great science and his fundamental humanity, still lives in the memory of many people.

Protective effects of Ceratonia siliqua extract on protamine gene expression, testicular function, and testicular histology in doxorubicin-treated adult rats: An experimental study.

BackgroundSpermatogenesis is a complex process that takes place under the influence of many different genes.ObjectiveThe aim of this study was to investigate the possible effects of Ceratonia siliqua hydroalcoholic extract (CSHAE) on protamine gene expression, testicular function, and testicular histology in doxorubicin-treated rats.Materials and Methods56 adult male rats with a age range of 2.5 to 3 months (210 10 gr) were divided into seven groups (n = 8/each). A) Control group was left untreated; B) Sham group received 0.3 ml distilled water intraperitoneally, C) Negative control group received 3 mg/kg doxorubicin, intraperitoneally once a week for 28 days; and D) Positive control group received 600 mg/kg of CSHAE orally for 48 days; E, F, G) the experimental groups 1, 2, and 3 received 150, 300, and 600 mg/kg of CSHAE respectively orally, for 48 days, as well as 3 mg/kg doxorubicin once a week for 28 days. Hematoxylin-eosin staining was used in the histological study of testes, and enzyme-linked immunosorbent assay method was used in measuring serum levels of testosterone. Protamine gene expression was determined by real-Time PCR method.ResultsThe mean body weight, testicular weight, testicular volume, testosterone level (p = 0.022), the count of Leydig, spermatogonia, spermatocyte, and spermatid cells, as well as protamine gene expression (p = 0.008) were significantly increased in the experimental group 2 compared to the negative control group. The regeneration of testicular tissue was observed in the experimental group 2.ConclusionCSHAE has protective effect on doxorubicin-induced testicular injuries.

Sperm parameters, DNA integrity, and protamine expression in patients with type II diabetes mellitus

Diabetes Mellitus (DM) is the most common endocrine disorder affecting many human physiological systems and tissues, including the reproductive organs in men. The age of individuals suffering from this disease has been falling rapidly in recent years. This study compared the effect of DM on sperm parameters, chromatin quality, and apoptosis, as well as the expression profile of protamine genes in men with and without DM using molecular and cytochemical assays. Sixty semen samples from the control group (N = 30) and case group (N = 30) were collected. There was a significant decrease in the percentages of sperm parameters in cases versus the controls (p˂0.05). Despite significantly higher percentages detected in spermatozoa with AB+, CMA3+, and TUNEL+, no change was demonstrated regarding protamines mRNA levels, as well as the P1/P2 ratios in cases in comparison with controls. In contrast, significant positive correlations were found between the quantity of P1 and P2 transcripts (r = 0.944, p < .001). The data indicated that DM not only caused a decrease in the quality of sperm parameters but also affected the sperm maturation process by increasing the substantial implications in the sperm DNA/chromatin levels of DM patients. IMPACT STATEMENT What is already known on this subject? Diabetes Mellitus (DM) is a chronic metabolic disorder affecting many human physiological systems and tissues, including the reproductive organs in men. The age of individuals suffering from this disease has been falling rapidly in recent years. What do the results of this study add? We found that DM not only caused a decrease in the quality of the sperm parameters, including motility and concentration, and an increase in morphological abnormalities but also affected the sperm maturation process by increasing the substantial implications in sperm DNA/chromatin levels of DM patients. Despite there being no significant difference in the mRNA levels of protamines between the two groups, our findings showed a positive correlation between the mRNA levels of P1 and progressive sperm motility. What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, chromatin and DNA assessments can have important implications for increasing fertility, as complementary tests, in combination with routine laboratory tests. Since sperm standard parameters are not capable of examining the condition of the sperm nucleus, men with abnormal sperm DNA can also have normal spermatogram, and diabetes is prevalent in reproductive age.

ZFP628 Is a TAF4b-Interacting Transcription Factor Required for Mouse Spermiogenesis.

TAF4b is a subunit of the TFIID complex that is highly expressed in the ovary and testis and required for mouse fertility. TAF4b-deficient male mice undergo a complex series of developmental defects that result in the inability to maintain long-term spermatogenesis. To decipher the transcriptional mechanisms upon which TAF4b functions in spermatogenesis, we used two-hybrid screening to identify a novel TAF4b-interacting transcriptional cofactor, ZFP628. Deletion analysis of both proteins reveals discrete and novel domains of ZFP628 and TAF4b protein that function to bridge their direct interaction in vitro Moreover, coimmunoprecipitation of ZFP628 and TAF4b proteins in testis-derived protein extracts supports their endogenous association. Using CRISPR-Cas9, we disrupted the expression of ZFP628 in the mouse and uncovered a postmeiotic germ cell arrest at the round spermatid stage in the seminiferous tubules of the testis in ZFP628-deficient mice that results in male infertility. Coincident with round spermatid arrest, we find reduced mRNA expression of transition protein (Tnp1 and Tnp2) and protamine (Prm1 and Prm2) genes, which are critical for the specialized maturation of haploid male germ cells called spermiogenesis. These data delineate a novel association of two transcription factors, TAF4b and ZFP628, and identify ZFP628 as a novel transcriptional regulator of stage-specific spermiogenesis.

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial.

ObjectiveSince sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL.MethodsTwenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment.ResultsSignificant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment.ConclusionDaily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

Effects of cryopreservation on stallion sperm protamine messenger RNAs.

Protamines substitute DNA-binding histones during late spermatogenesis in sperm nucleus. Stallion sperm contains all three variants of these arginine-rich and positively charged nuclear proteins (P1, P2 and P3). Two variants of protamine-2, that is P2 and P3, constitute approximately 15% of the entire protamine content. Also, the ratio of protamine-1 to protamine-2 varies among different mammalian species, and abnormal protamine ratios and protamine content are correlated with male infertility. In this study, changes in protamine mRNA abundance for all three protamines were investigated in stallion sperm during cryopreservation. Twelve ejaculates were collected from six sexually mature stallions. Sperm samples were divided into two parts for total mRNA extraction: one as fresh and the other as cryopreserved sample. Levels of three protamine transcripts were determined by real-time reverse transcriptase polymerase chain reaction. Results of relative expression showed that cryopreservation can significantly alter protamine transcripts: protamine 2 was downregulated, while protamine 3 was upregulated in cryopreserved samples relative to the control. Changes in protamine 1 were not significant after cryopreservation. This study is the first to evaluate changes in mRNA abundance of protamine genes in stallion sperm following cryopreservation. Such evaluations are important in finding transcriptomic markers for success in fertilization and assisted reproductivetechniques.

Influence of variation in global sperm DNA methylation level on the expression level of protamine genes and human semen parameters.

An infertility problem is a complex issue that affects 15% approximately of couples worldwide. The current study was designed to evaluate if there is a variation in the status of global DNA methylation among the study groups and to assess their impact on the protamine expression level and human semen parameters. Totalling 200 semen samples were collected from men (50 proved fertile, 60 normospermia and 90 oligospermia) with an average age of 34.9±4.3years. The DNA and RNA were isolated from purified spermatozoa; then, ELISA and qPCR were applied to estimate the status of global sperm DNA methylation and protamine expression level respectively. Besides that, the sperm chromatin decondensation and sperm DNA fragmentation were assessed. A significant variation was found in the global sperm DNA methylation and the protamine 1 and protamine 2 expression level among the study groups (p≤.001). Down-regulation has been found in the protamine 1 and protamine 2 expression levels in the oligospermia group compared to the proved fertile group with fold change (0.001 and 0.0002 respectively). In conclusion, this study proposes that the alteration in global DNA methylation may influence the protamine expression level and may be lead to abnormalities in human semen parameters.

Nuclear organization of the protamine locus

The human protamine gene cluster consists of three tightly regulated genes, protamine 1 (PRM1), protamine 2 (PRM2) and transition protein 2 (TNP2). Their products are required to repackage the paternal genome during spermiogenesis into a functional gamete. They reside within a single DNase I-sensitive domain associated with the sperm nuclear matrix, bounded by two haploid-specific Matrix Attachment Regions. The nuclear matrix is a dynamic proteinaceous network that is associated with both transcription and replication. While substantial effort has been directed toward pre- and post-transcriptional regulation, the role of the nuclear matrix in regulating haploid expressed genes has received comparatively little attention. In this regard, the functional organization of the human PRM1→PRM2→TNP2 cluster and where appropriate, comparisons to other model systems will be considered.

Polymorphisms of sperm protamine genes and CMA3 staining in infertile men with varicocele

ObjectivesThe aim of this study was to evaluate polymorphisms of sperm protamine genes and their effects on the result of CMA3 staining in varicocele men. Material and methodsIn a case control study, 128 patients with male infertility due to varicocele and 128 controls were recruited. Polymorphisms of PRM1 and PRM2 genes in extracted DNA samples were assessed by PCR-SSCP and sequencing. Protamine deficiency was also indirectly estimated by CMA3 staining. ResultNine different variants including six variants in PRM1 gene and three variants in PRM2 gene were found among varicocele patients. The results showed that sperm count, motility and morphology were significantly different between control group without gene variations and varicocele group who had several variations in their protamine genes (P<0.05). ConclusionTherefore, PRM1 and PRM2 variations in varicocele patients are associated with the production of spermatozoa with more protamine deficiency and this is one of the possible causes of infertility due to varicocele.

Genetic Polymorphisms in PRM1, PRM2, and YBX2 Genes are Associated with Male Factor Infertility.

The etiology of infertility is still unknown in almost half of all male infertility patients. In sperm, DNA condensation differs from somatic and female gamete cells, with the protamine (PRM) gene and its transcription factor, Y-box binding protein 2 (YBX2), playing key roles in making the structure more compact. Protamine polymorphisms have been studied in different populations, but various results have been acquired. In our study, we examined, for the first time in a Turkish population, the association between protamine gene alleles (PRM1 c.-190C>A, PRM1 c.197G>T, and PRM2 c.248C>T), and YBX2 (c.187T>C and c.1095 + 16A>G) and male infertility. This was accomplished using polymerase chain reaction-restriction fragment length polymorphism analyses of 100 infertile and 100 fertile Turkish men. Sperm DNA fragmentation analysis was performed using the Comet technique. We found that the AA and CA genotypes of the PRM1 c.-190C>A polymorphism had a significant association with infertility (p < 0.001) and the AA genotype was also highly significantly associated with high sperm DNA damage (p < 0.001). This study demonstrates that the PRM1 c.-190C>A polymorphism is associated with sperm DNA fragmentation, which may impact male infertility in the Turkish population. Further research with larger groups and in various other study populations will be required to clarify the impact of protamine and YBX2 gene polymorphisms on male infertility.

Polymorphisms of protamine genes contribute to male infertility susceptibility in the Chinese Han population.

Protamine (PRM) plays important roles in the packaging of DNA within the sperm nucleus. To investigate the role of PRM1/2 and transition protein 1 (TNP1) polymorphisms in male infertility, 636 infertile men and 442 healthy individuals were recruited into this case-controlled study of the Chinese Han population, using MassARRAY technology to analyze genotypes. Our analysis showed that there were no significant differences between controls and infertile cases among the five single nucleotide polymorphisms identified in PRM1, PRM2 and TNP1 [rs737008 (G/A), rs2301365 (C/A), rs2070923 (C/A), rs1646022 (C/G) and rs62180545 (A/G)]. However, we found that the PRM1 and PRM2 haplotypes GCTGC, TCGCA and TCGCC exhibited significant protective effects against male infertility compared to fertile men, while TCGGA, GCTCC and TCGGC represented significant risk factors for spermatogenesis. Our data showed that rs737008 and rs2301365 in PRM1, and rs1646022 in PRM2, were significantly associated with male infertility and that gene–gene interaction played a role in male infertility. A linkage disequilibrium plot for the five SNPs showed that rs737008 was strongly linked with both rs2301365 and rs2070923. These findings are likely to help improve our understanding of the etiology of male infertility. Further studies should include a larger number of genes and SNPs, particularly growing critical genes; such studies will help us to unravel the effect of individual genetic factors upon male infertility.

Investigation of Protamine Genes (PRM1, PRM2) Polymorphism and Its Impact on Sperm Toroid Integrity in Males from Ahmedabad (India)

Investigation of Protamine Genes (PRM1, PRM2) Polymorphism and Its Impact on Sperm Toroid Integrity in Males from Ahmedabad (India)