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   Table of Contents - Current issue
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May-June 2022
Volume 24 | Issue 3
Page Nos. 229-334

Online since Saturday, April 30, 2022

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INVITED EDITORIAL  

“Progressive motility” in elucidating novel genetic causes of male infertility p. 229
Feng Zhang
DOI:10.4103/aja202231  
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INVITED REVIEW Top

Genetic pathogenesis of acephalic spermatozoa syndrome: past, present, and future p. 231
Yu Wang, Ming-Fei Xiang, Na Zheng, Yun-Xia Cao, Fu-Xi Zhu
DOI:10.4103/aja202198  PMID:35074941
Acephalic spermatozoa syndrome (ASS) is one of the most severe spermatogenic failures of all infertility in men. The cognition of ASS has experienced a tortuous process. Over the past years, with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies, the unraveling of the genetic causes of spermatogenic failure has become highly active. From these advances, we established a genetic background and made significant progress in the discovery of the genetic causes of ASS. It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome. In this review, we enumerate various technological developments, which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present. Simultaneously, we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present. Furthermore, we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.
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The roles of intraflagellar transport (IFT) protein 25 in mammalian signaling transduction and flagellogenesis p. 238
Yong-Hong Man, Isabella Warmbrunn, Ling Zhang, Zhi-Bing Zhang
DOI:10.4103/aja202179  PMID:34747727
Cilium, an organelle with a unique proteome and organization, protruding from the cell surface, generally serves as a force generator and signaling compartment. During ciliogenesis, ciliary proteins are synthesized in cytoplasm and transported into cilia by intraflagellar transport (IFT) particles, where the inner counterparts undergo reverse trafficking. The homeostasis of IFT plays a key role in cilial structure assembly and signaling transduction. Much progress has been made on the mechanisms and functions of IFT; however, recent studies have revealed the involvement of IFT particle subunits in organogenesis and spermatogenesis. In this review, we discuss new concepts concerning the molecular functions of IFT protein IFT25 and how its interactions with other IFT particle subunits are involved in mammalian development and fertility.
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INVITED ORIGINAL ARTICLE Top

From azoospermia to macrozoospermia, a phenotypic continuum due to mutations in the ZMYND15 gene p. 243
Zine-Eddine Kherraf, Caroline Cazin, Florence Lestrade, Jana Muronova, Charles Coutton, Christophe Arnoult, Nicolas Thierry-Mieg, Pierre F Ray
DOI:10.4103/aja202194  PMID:35017390
Thanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (AURKC gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia. AURKC analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (ZMYND15 gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man, ZMYND15 has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic ZMYND15 variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in ZMYND15 can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific AURKC or dpy-19 like 2 (DPY19L2) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES.
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Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing p. 248
Matthew Hoi Kin Chau, Ying Li, Peng Dai, Mengmeng Shi, Xiaofan Zhu, Jacqueline Pui Wah Chung, Yvonne K Kwok, Kwong Wai Choy, Xiangdong Kong, Zirui Dong
DOI:10.4103/aja2021106  PMID:35017386
Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.
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A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms p. 255
Muhammad Zubair, Ranjha Khan, Ao Ma, Uzma Hameed, Mazhar Khan, Tanveer Abbas, Riaz Ahmad, Jian-Teng Zhou, Wasim Shah, Ansar Hussain, Nisar Ahmed, Ihsan Khan, Khalid Khan, Yuan-Wei Zhang, Huan Zhang, Li-Min Wu, Qing-Hua Shi
DOI:10.4103/aja2021122  PMID:35259782
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
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Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology p. 260
Tian-Ying Yang, Ying Chen, Guo-Wu Chen, Yi-Si Sun, Zhi-Chao Li, Xiao-Rong Shen, Yi-Ni Zhang, Wen He, Dan Zhou, Hui-Juan Shi, Ai-Jie Xin, Xiao-Xi Sun
DOI:10.4103/aja2021111  
Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
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CRISPR/Cas9-mediated genome editing reveals 12 testis-enriched genes dispensable for male fertility in mice p. 266
Yuki Oyama, Haruhiko Miyata, Keisuke Shimada, Yoshitaka Fujihara, Keizo Tokuhiro, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa
DOI:10.4103/aja.aja_63_21  PMID:34290169
Gene expression analyses suggest that more than 1000–2000 genes are expressed predominantly in mouse and human testes. Although functional analyses of hundreds of these genes have been performed, there are still many testis-enriched genes whose functions remain unexplored. Analyzing gene function using knockout (KO) mice is a powerful tool to discern if the gene of interest is essential for sperm formation, function, and male fertility in vivo. In this study, we generated KO mice for 12 testis-enriched genes, 1700057G04Rik, 4921539E11Rik, 4930558C23Rik, Cby2, Ldhal6b, Rasef, Slc25a2, Slc25a41, Smim8, Smim9, Tmem210, and Tomm20l, using the clustered regularly interspaced short palindromic repeats /CRISPR-associated protein 9 (CRISPR/Cas9) system. We designed two gRNAs for each gene to excise almost all the protein-coding regions to ensure that the deletions in these genes result in a null mutation. Mating tests of KO mice reveal that these 12 genes are not essential for male fertility, at least when individually ablated, and not together with other potentially compensatory paralogous genes. Our results could prevent other laboratories from expending duplicative effort generating KO mice, for which no apparent phenotype exists.
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INVITED COMMENTARY Top

Commentary on “CRISPR/Cas9-mediated genome editing reveals 12 testis-enriched genes dispensable for male fertility in mice” p. 273
Brendan J Houston
DOI:10.4103/aja202196  PMID:34810375
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REVIEW Top

Endocrine aberrations of human nonobstructive azoospermia p. 274
Yong Tao
DOI:10.4103/aja202181  PMID:35042310
Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic–pituitary–testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.
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ORIGINAL ARTICLES Top

Intrauterine insemination with donor sperm: only the number of motile spermatozoa inseminated influences both pregnancy and live-birth rates p. 287
Marie Cardey-Lefort, Berengere Ducrocq, Audrey Uk, Helen Behal, Anne-Laure Barbotin, Geoffroy Robin
DOI:10.4103/aja202149  PMID:34596599
Intrauterine insemination with donor sperm (IUI-D) is an assisted reproductive technology (ART) offered to couples with definitive male infertility or risk of genetic disease transmission. Here, we sought to evaluate our practice in IUI-D and identify factors that influenced the success rate. We performed a retrospective, single-center study of all IUI-D procedures performed at Lille University Medical Center (Lille, France) between January 1, 2007, and December 31, 2017. Single and multivariate analyses with a mixed logistic model were used to identify factors associated with clinical pregnancies and live births. We included 322 couples and 1179 IUI-D procedures. The clinical pregnancy rate was 23.5%, and the live birth rate was 18.9% per IUI-D. In a multivariate analysis, the women's age was negatively associated with the live birth rate. The number of motile spermatozoa inseminated was the only factor associated with both clinical pregnancies and live births, with a chosen threshold of 0.75 million. The clinical pregnancy and live birth rates were, respectively, 17.3% and 13.0% below the number of motile spermatozoa inseminated threshold and 25.9% and 21.0% at or above the threshold (all P = 0.005). The number of motile spermatozoa inseminated was the only factor that significantly influenced both pregnancies and live-birth rates after IUI-D. Indeed, below a threshold of 0.75 million motile spermatozoa inseminated, those rates were significantly lower. Application of this number of motile spermatozoa inseminated threshold may help centers to allocate donations more effectively while maintaining reasonable waiting times for patients.
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Effects of plication procedures in special cases of Peyronie's disease: a single-center retrospective study of 72 patients p. 294
Wen Ji Li, Jie-Wen Bao, Jian-Hua Guo, Da-Chao Zheng, Min-Kai Xie, Zhong Wang
DOI:10.4103/aja202219  PMID:35381692
General recommendations regarding surgical techniques are not always appropriate for all Peyronie's disease (PD) patients. Therefore, the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities. The clinical data from 72 patients who underwent plication procedures were analyzed in this study. Patients were divided into Groups A and B according to the curvature severity (≤60° or >60°) and Groups 1 and 2 according to the duration of disease stabilization (≥3 months or <3 months). At the 1-year follow-up, 90.0% (36/40) and 90.6% (29/32) patients reported complete penile straightening, and 60.0% (24/40) and 100.0% (32/32) patients reported penile shortening in Groups A and B, respectively. No curvature recurrence occurred in any patient, and no significant differences were observed in postoperative International Index of Erectile Function–Erectile Function domain (IIEF-EF), erectile pain, sensitivity, or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization. However, the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2 (mean ± standard deviation [s.d.]: 20.9 ± 2.0 months and 14.3 ± 1.2 months, respectively, P < 0.001). The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature. In addition, the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.
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Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity p. 299
Ping Ping, Zhong Zheng, Yi Ma, Sha-Sha Zou, Xiang-Feng Chen
DOI:10.4103/aja202151  PMID:34677147
The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.
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The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer: a real-world study from the SEER database p. 305
Qi-Ming Yuan, Tian-Hai Lin, Kun Jin, Shi Qiu, Xiang-Hong Zhou, Di Jin, Jia-Kun Li, Lu Yang, Qiang Wei
DOI:10.4103/aja202159  PMID:34596600
To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02–1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23–4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92–1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24–6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.
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Application of the Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair p. 311
Qi-Gen Xie, Kai Xia, Xiang-Ping Li, Peng Luo, Zuo-Qing Li, Cheng Su, Chun-Hua Deng
DOI:10.4103/aja202163  PMID:34677148
Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
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Association of sexually transmitted infection with semen quality in men from couples with primary and secondary infertility p. 317
Shun Bai, Yuan Li, Mei-Hong Hu, Li Wu, Li-Jun Shui, Xiao-Han Wang, Yi-Xun Liu, Qiu-Ling Yue, Li-Na Yu, Kai-Qiang Fu, Xian-Hong Tong, Xue-Chun Hu, Bo Xu
DOI:10.4103/aja202164  PMID:34782548
This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
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Effect of thermophilic bacterium HB27 manganese superoxide dismutase in a rat model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) p. 323
Nai-Wen Chen, Jing Jin, Hong Xu, Xue-Cheng Wei, Ling-Feng Wu, Wen-Hua Xie, Yu-Xiang Cheng, Yi He, Jin-Lai Gao
DOI:10.4103/aja202157  PMID:34747725
We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague–Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS.
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LETTER TO THE EDITOR Top

Novel treatment for post-orgasmic illness syndrome: a case report and literature review p. 332
Tian-Bao Huang, Jun-Jie Yu, Yong-Jun Du, Zhi-Yong Liu
DOI:10.4103/aja202170  PMID:34747723
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