Role In Male Infertility Research Articles

CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients.

Congenital bilateral absence of vas deferens (CBAVD) is a urological syndrome of Wolffian ducts and is responsible for male infertility and obstructive azoospermia. This study is designed to explore the integrity of exon 10 of CFTR and its role in male infertility in a cohort of CBVAD patients in Pakistan. Genomic DNA was extracted from 17 male patients with CBAVD having clinical symptoms, and 10 healthy controls via phenol-chloroform method. Exon 10 of the CFTR gene was amplified, using PCR with specific primers and DNA screening was done by Sanger sequencing. Sequencing results were analyzed using freeware Serial Cloner, SnapGene, BioEdit and FinchTV. Furthermore, bioinformatics tools were used to analyze the mutations and their impact on the protein function and stability. We have identified 4 mutations on exon 10 of CFTR in 6 out of 17 patients. Two of the mutations were missense variants V456A, K464E, and the other two were silent mutations G437G, S431S. The identified variant V456A was present in 4 of the studied patients. Whereas, the presence of K464E in our patients further weighs on the crucial importance for its strategic location to influence the gene function at post-transcriptional and protein level. Furthermore, Polyphen-2 and SIFT analyze the mutations as harmful and deleterious. The recurrence of V456A and tactically conserved locality of K464E are evidence of their potential role in CBAVD patients and in male infertility. The data can contribute in developing genetic testing and treatment of CBAVD.

Assessment of sperm chromosomal abnormalities using fluorescence in situ hybridization (FISH): implications for reproductive potential.

Chromosomal abnormalities play an important role in male infertility, which is becoming a significant issue in human fertility. Aim of this study was to evaluate the incidence of spermatic aneuploidies and diploidies in human sperm, according to semen parameters. We performed semen analysis according to the 6th edition of WHO criteria in 50 male subjects; samples weredivided into normozoospermic (n = 23) or thosewith altered seminal parameters (n = 27). To assess chromosomal numerical alterations of sperm, fluorescence in situ hybridization (FISH) was used. A significant increase in aneuploidies and diploidies was observed in samples with altered seminal parameters. Furthermore, stratifying this group, we observed a significant increase in aneuploidies and total abnormalities in oligozoospermic, asthenoteratozoospermic (AT), and oligoteratoasthenozoospermic (OAT) samples compared to normozoospermic. Our results showed the correlation between altered seminal parameters and numerical chromosomal abnormalities, confirming that sperm FISH analysis could be an additional clinical tool to assess reproductive potential in infertile males. Moreover, our results point to the importance of updating the normality ranges for detecting chromosomal aneuploidies using FISH.

Role of pyridoxine and oxidative stress in asthenozoospermia

PurposeInfertility is a worldwide concern, and recent research indicates that vitamin B6 deficiency may play a role in male infertility, primarily by inducing hyperhomocysteinemia and oxidative stress. These processes can have a detrimental effect on semen quality, ultimately affecting male fertility. Here, we aim to evaluate the biochemical status of pyridoxine (vitamin B6) in relation to total glutathione and total antioxidant capacity. Materials and methodsA case control study samples were collected of asthenozoospermic (n = 63) and normospermic (n = 43) cases, with average men age 30.35 ± 7.03 years old. Semen plasma specimens representing both fertile and sub-fertile men visiting two different secondary care health institute in Irbid province, Jordan. All samples were assessed according to WHO guidelines (2021) and by using spectrophotometry to evaluate the semen plasma levels of vitamin B6, glutathione (GSH) and total antioxidant capacity (TAC). ResultsOur main finding is there is significant positive correlations between the seminal plasma concentration of GSH (p < 0.0001) and TAC (p < 0.0073) are significantly correlated with vitamin B6 deficiency in asthenozoospermia group in comparison to normozoospermia cases. A significant decrease (p < 0.0001) the levels of vitamin B6 in men with asthenozoospermia compared to normozoospermic men (control) with an approximate 80 % percent reduction in the mean levels between groups. ConclusionsThese findings suggest that pyridoxine deficiency may very well alter the GSH system, in so doing affecting the antioxidant defense mechanism against reactive oxygen species to sperm, impacting sperm development and maturation. leading to asthenozoospermia.

Thyroid Hormones and Their Role in Male Infertility: A Comprehensive Review

Thyroid hormones are pivotal regulators of various physiological processes, including reproductive function. While the impact of thyroid dysfunction on female fertility has been extensively studied, its association with male infertility has gained increasing recognition. This comprehensive review explores the role of thyroid hormones in male infertility, focusing on their effects on spermatogenesis, sperm quality, and reproductive outcomes. The review delves into the physiology of thyroid hormones, the presence of thyroid hormone receptors in the male reproductive system, and the influence of thyroid dysfunction on spermatogenesis and semen parameters. Additionally, it examines the molecular mechanisms underlying thyroid hormone action in the male reproductive system and discusses potential therapeutic strategies targeting thyroid hormone pathways to improve male fertility. Understanding the intricate relationship between thyroid hormones and male infertility is crucial for advancing diagnostic and therapeutic approaches in the management of male infertility associated with thyroid dysfunction.

Heat stress upregulates arachidonic acid to trigger autophagy in sertoli cells via dysfunctional mitochondrial respiratory chain function

As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility.

Identification of a new mutation in the ACTL9 gene in men with unexplained infertility.

Infertility is defined as the failure to achieve pregnancy after one year of unprotected intercourse within a marital relationship. Approximately 10%-15% of couples worldwide experience infertility issues, with nearly half of these cases attributed to male factors. Among men with unexplained infertility, genetic mutations have been identified as a potential cause. Studies have indicated that mutations affecting the function of the protein encoded by the ACTL9 gene may play a role in male infertility. The purpose of this research was to identify mutations in the ACTL9 gene associated with male infertility in a sample of 40 infertile men with unknown causes. Genomic DNA extraction and PCR amplification were carried out on samples from each individual. The genetic material was then analyzed using Sanger sequencing, followed by bioinformatics and segregation analysis to determine the potential effects of the observed variations. A novel genetic variant, c.376G>A (p.Glu126Lys), was identified in an infertile male individual, representing a previously unreported finding that was validated through segregation analyses. This specific variant induces a change from glutamate to lysine at the amino acid level by replacing the nucleotide G with A in the genomic DNA sequence, consequently impacting the secondary structure and function of the protein. The conclusive analysis of the procedure indicated that this alteration has the potential to interfere with the process of fertilization, ultimately resulting in the complete failure of fertilization (TFF) and causing male infertility.

Inside Front Cover: Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility (View 2/2024)

Inside Front Cover: Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility (View 2/2024)

A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility.

To investigate the genetic etiology of patients with female infertility. Whole Exome Sequencing was performed on genomic DNA extracted from the patient's blood. Exome data were filtered for damaging rare biallelic variants in genes with possible roles in reproduction. Sanger sequencing was used to validate the selected variants and segregate them in family members. A novel homozygous likely pathogenic variant, c.626G>A, p.Trp209*, was identified in the TERB1 gene of the patient. Additionally, we report a second homozygous pathogenic TERB1 variant, c.1703C>G, p.Ser568*, in an infertile woman whose azoospermic brother was previously described to be homozygous for her variant. Here, we report for the first time two homozygous likely pathogenic and pathogenic TERB1 variants, c.626G>A, p.Trp209* and c.1703C>G, p.Ser568*, respectively, in two unrelated women with primary infertility. TERB1 is known to play an essential role in homologous chromosome movement, synapsis, and recombination during the meiotic prophase I and has an established role in male infertility in humans. Our data add TERB1 to the shortlist of Meiosis I genes associated with human infertility in both sexes.

Super‐resolution ultrasound localization microscopy for the non‐invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility

AbstractTesticular microcirculation is closely related to spermatogenic function and seminiferous tubular function. The diagnosis and monitoring of testicular diseases can be associated with testicular microcirculation; however, there are currently no effective non‐invasive methods for super‐resolution imaging of testicular microcirculation. In this study, we introduced state‐of‐the‐art graph‐based tracking with the Kalman motion model algorithm to non‐invasively image human testicular microcirculation for the first time with a regular frame‐rate clinical ultrasound imaging system (37 Hz). Two distinct testicular vessels with an 81 µm separation were resolved in the testicular vasculature, surpassing all other imaging modalities. In a retrospective study, we performed contrast‐enhanced ultrasound examinations(CEUS) and ultrasound localization microscopy (ULM) processing on the included 76 infertile patients and 15 healthy controls from August 2021 to May 2023 and obtained super‐resolution images of testicular microcirculation with sub‐diffraction resolution. Through the results of one‐way analysis of variance tests and receiver operating characteristic analyses, we found that the ULM‐based parameters hold promise as clinical guidance for differentiating between non‐obstructive and obstructive male infertility. The mean vessel diameter achieved an area under the curve (AUC) of 0.920 (95% confidence interval [CI]: 0.847–0.994, p &lt; .001) with a cut‐off value of 170.9 µm in oligoasthenospermia, and an AUC of 0.952 (95% CI: 0.875–1.000, p &lt; .001) with a cut‐off value of 169.9 µm in azoospermia patients, respectively, addressing a significant clinical challenge.

#97 : Can Platelet Rich Plasma (PRP) Improve Human Ejaculated Sperm Quality? A Systematic Review and Meta Analysis

Background and Aims: Males are found contribute to 50% of infertility cases overall. Abnormal sperm parameters, such as low concentration, low motility, or abnormally morphology is thought to play a major role in male infertility. In many recent studies, Platelet Rich Plasma (PRP) was reported to have potential therapeutic effect. PRP with its rich growth factor composition, has already proven beneficial in regenerative therapy. PRP can improve the structural and functional impairment of the testis, thereby improve the sperm quality as its product. This study aims to identify the improvement of ejaculated sperm concentration, motility, morphology after treatment with PRP. Methods: A systematic search was conducted in PubMed, Cochrane and Google Scholar databases up to November 2022. We used Prisma’s checklist 2020 as a guideline for writing this. To be included in this meta-analysis, eligible studies had to be a clinical trial comparing ejaculated sperm with PRP treatment and no PRP addition. We conducted both quantitative and qualitative analysis of the assessed outcomes. Results: A total of 91 studies were retrieved. After excluding ineligible publication, 5 studies were finally included in the present meta-analysis (n=331). Among them, varied methods of PRP intervention, but all of them had using PRP 2%. By using a random effect model, there is an improvement of the progressive sperm in group with PRP treatment (MD 15,00, 95%-CI 6,71-23,29). Quantitative analysis (meta-analysis) was not carried out for sperm concentration and morphology, but was explained descriptively, that sperm concentration and morphology increased after PRP treatment. The articles included in the analysis have a low risk of bias. Conclusions: There is an improvement in sperm progressivity after treatment with PRP, that also means there is an improvement in human ejaculated sperm quality. Although found beneficial enhancing the sperm progressivity, but still needed strong evidence for further research.

Kualitas Sperma pada Laki-Laki Defisiensi Vitamin D di Palembang

Vitamin D deficiency may play some roles in male infertility. Abundant vitamin D receptors exist in male reproductive tracts, implying some significant functions of vitamin D in spermatogenesis and/or testosterone synthesis. This study aims to measure sperm parameters in males with vitamin D deficiency in Palembang, South Sumatra. This study was a conducted as observational, cross-sectional descriptive study on single mother and child hospital in Palembang. Subjects’ serum vitamin D was measured in an accredited external clinical laboratory and sperm samples were collected and examined in same laboratory according to standard protocols. Median age of subject was 30,0 (24-49) years old. Mean serum vitamin D concentration was 21.372 ± 4.202 ng/mL. Median sperm concentration was 21.75 (0.00-137.00) millions/mL. Median sperm count was 66.14 (0.00-370.80) millions. Average progressive motility was 35.64 ± 18.573%. Median normal morphology was 5.00 (0.00-7.00)%. Normal sperm parameters observed in this study implicated vitamin D plays no significant role in sperm quality.

Correlation between LHCGR and NR5A1 genes polymorphism and male infertility risk

IntroductionInfertility is one of the important phenomena in human reproduction. Genetic factors are the most important cause of male infertility. Here, we aimed to investigate the correlation between idiopathic male infertility and SNPs of the LHCGR (rs2293275) and NR5A1 (rs1057517779) genes in the Iranian-Azeri population. MethodsThis case-control study consisted of 100 males with infertility and 100 healthy males from the Iranian Azeri population. Genomic DNA isolation from whole blood samples and Tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) method was used for genotyping. The data analysis was performed by chi-square (χ2) and Fisher’s exact tests. ResultsGenotyping analysis for LHCGR (rs2293275) polymorphism indicated that the frequency of C in the case group was significantly higher than in the control group (P < .05). Moreover, genotyping analysis for NR5A1 (rs1057517779) polymorphism indicated that the frequencies of the A allele and heterozygote GA genotype in the case group were significantly higher than those in the control group (P < .05). ConclusionOur study demonstrated that the SNPs of LHCGR (rs2293275) and NR5A1 (rs1057517779) genes may play a critical role in male infertility in the Iranian Azeri population. However, further studies on other ethnic origins with larger sample sizes are essential for accessing more accurate results. Moreover, functional experiments might be needed to understand the role of these polymorphisms in the molecular pathways involved in male fertility.

Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs' Role in Male Infertility.

Male infertility is a global health issue, affecting over 20 million men worldwide. Genetic factors are crucial in various male infertility forms, including teratozoospermia. Nonetheless, the genetic causes of male infertility remain largely unexplored. In this study, we employed whole-genome sequencing and RNA expression analysis to detect differentially expressed (DE) long-noncoding RNAs (lncRNAs) in teratozoospermia, along with mutations that are exclusive to teratozoospermic individuals within these DE lncRNAs regions. Bioinformatic tools were used to assess variants' impact on lncRNA structure, function, and lncRNA-miRNA interactions. Our analysis identified 1166 unique mutations in teratozoospermic men within DE lncRNAs, distinguishing them from normozoospermic men. Among these, 64 variants in 23 lncRNAs showed potential regulatory roles, 7 variants affected 4 lncRNA structures, while 37 variants in 17 lncRNAs caused miRNA target loss or gain. Pathway Enrichment and Gene Ontology analyses of the genes targeted by the affected miRNAs revealed dysregulated pathways in teratozoospermia and a link between male infertility and cancer. This study lists novel variants and lncRNAs associated for the first time with teratozoospermia. These findings pave the way for future studies aiming to enhance diagnosis and therapy in the field of male infertility.

Correlación entre el polimorfismo de los genes LHCGR y NR5A1y el riesgo de infertilidad masculina

IntroductionInfertility is one of the important phenomena in human reproduction. Genetic factors are the most important cause of male infertility. Here, we aimed to investigate the correlation between idiopathic male infertility and SNPs of the LHCGR (rs2293275) and NR5A1 (rs1057517779) genes in the Iranian-Azeri population. MethodsThis case-control study consisted of 100 males with infertility and 100 healthy males from the Iranian Azeri population. Genomic DNA isolation from whole blood samples and Tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) method was used for genotyping. The data analysis was performed by Chi-square (χ2) and Fisher's exact tests. ResultsGenotyping analysis for LHCGR (rs2293275) polymorphism indicated that the frequency of C in the case group was significantly higher than in the control group (P<.05). Moreover, genotyping analysis for NR5A1 (rs1057517779) polymorphism indicated that the frequencies of the A allele and heterozygote GA genotype in the case group were significantly higher than those in the control group (P<.05). ConclusionOur study demonstrated that the SNPs of LHCGR (rs2293275) and NR5A1 (rs1057517779) genes may play a critical role in male infertility in the Iranian Azeri population. However, further studies on other ethnic origins with larger sample sizes are essential for accessing more accurate results. Moreover, functional experiments might be needed to understand the role of these polymorphisms in the molecular pathways involved in male fertility.

Statistical methods to detect mother-father genetic interaction effects on risk of infertility: A genome-wide approach.

Infertility is a heterogeneous phenotype, and for many couples, the causes of fertility problems remain unknown. One understudied hypothesis is that allelic interactions between the genotypes of the two parents may influence the risk of infertility. Our aim was, therefore, to investigate how allelic interactions can be modeled using parental genotype data linked to 15,789 pregnancies selected from the Norwegian Mother, Father, and Child Cohort Study. The newborns in 1304 of these pregnancies were conceived using assisted reproductive technologies (ART), and the remainder were conceived naturally. Treating the use of ART as a proxy for infertility, different parameterizations were implemented in a genome-wide screen for interaction effects between maternal and paternal alleles at the same locus. Some of the models were more similar in the way they were parameterized, and some produced similar results when implemented on a genome-wide scale. The results showed near-significant interaction effects in genes relevant to the phenotype under study, such as Dynein axonemal heavy chain 17 (DNAH17) with a recognized role in male infertility. More generally, the interaction models presented here are readily adaptable to the study of other phenotypes in which maternal and paternal allelic interactions are likely to be involved.

Hyperhomocysteinemia lowers serum testosterone concentration via impairing testosterone production in Leydig cells.

Hyperhomocysteinemia (HHcy) plays a salient role in male infertility. However, whether HHcy interferes with testosterone production remains inconclusive. Here, we reported a lower serum testosterone level in HHcy mice. Single-cell RNA sequencing revealed that genes related to testosterone biosynthesis, together with nuclear receptor subfamily 5 group A member 1 (Nr5a1), a key transcription factor for steroidogenic genes, were downregulated in the Leydig cells (LCs) of HHcy mice. Mechanistically, Hcy lowered trimethylation of histone H3 on lysine 4 (H3K4me3), which was bound on the promoter region of Nr5a1, resulting in downregulation of Nr5a1. Intriguingly, we identified an unknown cell cluster annotated as Macrophage-like Leydig cells (McLCs), expressing both LCs and macrophages markers. In HHcy mice, McLCs were shifted toward pro-inflammatory phenotype and thus promoted inflammatory response in LC. Betaine supplementation rescued the downregulation of NR5A1 and restored the serum testosterone level in HHcy mice. Overall, our study highlights an etiological role of HHcy in LCs dysfunction.

Susceptibility to azoospermia by haplotype analysis of protamine 1 and protamine 2 variants

Infertility remains a major global problem, affecting 10–15% of couples worldwide, with half of the cases due to male factors. Protamines, found only in the testes, are essential for sperm chromatin condensation and paternal genome imprinting during spermatogenesis. Seventy testicular samples from infertile men were analyzed for the expression level of PRM1 and PRM2. 448 infertile males were additionally examined for PRM1 and PRM2 polymorphism. There was a significant association of rs2070923 polymorphism of PRM2 in both additive and recessive models (OR (95% CI) 1.32[0.92; 1.88, p = 0.023] and 2.26[1.12; 4.57, p = 0.017], respectively). The TT genotype of rs2070923 PRM2 was also correlated with lower gene expression of PRM2 in the infertile group (p = 0.03). Moreover, our result showed that the frequency of GTCT haplotype was higher than average in azoospermic patients (OR = 2.67; 95%CI = 1.17–2.53; p = 0.041) and that gene-gene interaction played a role in male infertility. The linkage disequilibrium plot showed that rs2301365 was strongly associated with rs2070923. For the first time, we reported a significant haplotype of PRM1 and PRM2 genes associated with male infertility in Iranian population. These results are likely to contribute to a better understanding of the causes of male infertility.

P-082 Estradiol levels in idiopathic male infertility

Abstract Study question Investigating estradiol in relation with other sperm parameters might reveal new correlations which would help our understanding of male idiopathic infertility Summary answer Statistical significance was found in a series of correlations of E2 levels and sperm, hormonal and health parameters What is known already Male infertility is a rising major health concern, with sperm counts decreasing by 50-60% in the recent decades. The causes for male infertility are very different (genetic, systemic, neurological, infections, trauma, etc.), but at least 44% of cases are idiopathic. Estradiol (E2) regulates spermatogenesis by binding to classical intracellular estrogen receptors or membrane estrogen receptors to trigger genomic and nongenomic signal transduction pathways. Although E2 doesn’t carry any prognostic value by itself, as its levels don’t vary significantly between infertile and fertile men, its association with other parameters may lead to a better understanding of male infertility Study design, size, duration the design of cross-sectional study comprising 111 subjects- 87 infertile patients (median: 34 years, range 20–55 years) and 24 control (median: 33 years, range 20–45 years). The subjects were included in this study during 3 years (between October 2019- September2022). Inclusion criteria: spermatic parameters according to WHO 2010 Standards Exclusion criteria: Radiotherapy and/or pelvic chemotherapy (over the last 6 months), known genetic aberrations, endocrine diseases, urogenital infections, bilateral orchiectomy, vasectomy and occupational exposure. Participants/materials, setting, methods Infertile men were grouped in azoospermia (AZOO), oligoasthenoteratozoospermia (OATS/OATSS) and oligoasthenozoospermia (OAS/OASS). Blood and semen samples were collected and E2 levels were measured in both seminal and blood samples, along with sperm parameters (sperm count, motility, morphology) and other factors (BMI, hormone and vitamin D levels, BsmI polymorphism in the vitamin D receptor gene) were evaluated. E2 levels were assayed using the electrochemiluminescence method with the RocheCobas E601 autoanalyzer. Main results and the role of chance E2 varies slightly between the different patients’ groups, the highest values being found in the OAT/OATSS group. BMI is higher in the infertile group; significant higher values were found for the OAS/OASS (p = 0.002) and OATS/OATS (p = 0.017) groups. Statistical analysis has revealed a significant difference between serum and seminal E2 levels in each group (AZOO p = 0.0355; OATS/OATSS p = 0.0156; control p = 0.0009), but also between OATS/OATSS seminal group and control seminal group (p = 0.0366). The E2/Inhibin ratio presented higher values in patients with OATS/OATSS (p = 0.0031) and azoospermia (p = 0.0059). The lowest values of E2/Vitamin D ratio were detected in the OAS/OASS and OATS/OATSS groups (p = 0.0254), A significant increase of E2 serum level was observed in patients from the OATS/OATSS group in the case of homozygous for mutant allele of BsmI polymorphism (p = 0.0419). The results bring new evidence regarding the role of E2 in male infertility. The obtained data indicates an interplay between E2 and Inhibin B and vitamin D serum levels, highlighting it’s the role in male infertility. Limitations, reasons for caution The study could be extended to a larger population sample, in order to further validate the obtained results Wider implications of the findings Estradiol activity plays an important role in male fertility and along with the investigated parameters could serve as potential markers in the diagnosis and management of male infertility. Trial registration number PN-III-P2-2.1-PED-2019-4402

Next-generation sequencing analysis of semen microbiome taxonomy in men with nonobstructive azoospermia vs. fertile controls: a pilot study

To study how the semen microbiome profile in men with nonobstructive azoospermia (NOA) differs from that of fertile controls (FCs). Using quantitative polymerase chain reaction and 16S ribosomal RNA, we sequenced semen samples from men with NOA (follicle-stimulating hormone >10 IU/mL, testis volume <10 mL) and FCs and performed a comprehensive taxonomic microbiome analysis. All patients were identified during evaluation at the outpatient male andrology clinic at the University of Miami. In total, 33 adult men, including 14 diagnosed with NOA and 19 with proven paternity undergoing vasectomy, were enrolled. Bacterial species in the semen microbiome were identified. Alpha-diversity was similar between the groups, suggesting similar diversity within samples, whereas beta-diversity was different, suggesting differences in taxa between samples. In the NOA men, the phyla Proteobacteria and Firmicutes were underrepresented, and Actinobacteriota were overrepresented compared with FC men. At the genus level, Enterococcus was the most common amplicon sequence variant in both groups, whereas 5 genera differed significantly between the groups, including Escherichia and Shigella, Sneathia, and Raoutella. Our study showed significant differences in the seminal microbiome between men with NOA and fertile men. These results suggest a loss of functional symbiosis may be associated with NOA. Further research into the characterization and clinical utility of the semen microbiome and its causal role in male infertility is necessary.

(333) Association Between TNP2 G1272C Polymorphism and Human Male Infertility: A Meta-analysis

Abstract Introduction Infertility is defined as the incapability to achieve fertilization after 1 year following sexual intercourse without any contraceptive measure. Poor sperm quality contributes to 90% of male infertility. Spermatogenesis takes place in the seminiferous tubules of the testis by proliferation followed by complex morphologic, physiologic, and biochemical modifications that result in the formation of mature spermatozoa. These specific events are supported by spermiogenesis-specific gene products. During spermiogenesis, sperm chromatin undergoes a series of modifications in which histones are lost and replaced with transition proteins and subsequently with protamine. Replacement of histones to protamine is impotent in the formation of mature spermatozoa. Histones are important for DNA replication but in spermatogenesis histones replacement with protamine prevents DNA replication and causes sperm maturation. Any problem in this replacement may cause male infertility. The nuclei of elongated and condensing spermatids contain nuclear transition protein 1 (TNP1) and nuclear transition protein 2 (TNP2) but tnp2 is more effective. TNP2 plays a critical role in shaping sperm nucleus, displacement of histones with protamine condensation of chromatin, and binding of protamines to DNA. Objective This review aims to determine the association of a TNP2 polymorphism (G1272C) with the risk of male infertility. Methods PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding TNP2 polymorphism (G1272C) and male infertility were selected for this meta-analysis. Results Based on literature search and inclusion criteria, 3 case-control studies out of the total 16 articles were selected, ranging from 2005 to 2019. The included case-control studies observing G1272C polymorphism in the TNP2 gene contained 534 cases and 516 controls. No significant association (p &amp;gt; 0.05) between G1272 polymorphism and male infertility was found, based on all of the three genetic models. Whereas, when we pooled the data of two population of same region i.e. Iran, significant association (p &amp;lt; 0.05) was found between G1272C polymorphism and male infertility on the basis of additive model (CC vs GG: OR= 0.34, 95% CI [0.20-0.56], I2 = 81%), dominant model (CC+CG vs GG: OR= 0.46, 95% CI [0.32-6.67], I2 = 91%) &amp; recessive model (CC vs CG + GG: OR= 0.48, 95% CI [0.31-0.76], I2 = 85%), showing that this polymorphism might contribute to the male infertility, depending upon the ethnicity. Conclusions TNP2 G1272C may play role in male infertility suggested by the significant association in the Iranian population. Disclosure No