OBJECTIVETo investigate the changes in seminal paraoxonase-1 (PON-1) activity in infertile male patients and assess the clinical value of seminal PON-1 examination in the diagnosis of male infertility.

METHODSSeminal PON-1 activity was detected by spectrophotometric method in the semen samples from 270 infertile male patients and 50 health fertile males (control), and the semen parameters were analyzed using a computer-assisted semen analysis system.

RESULTSIn the male infertility group, seminal PON-1 activity was 1.22∓0.76 U/L in the patients with normal semen parameters and 0.64∓0.54 in the patients with abnormal semen parameters, both significantly lower than that of the control group (3.17∓0.89 U/L, P<0.01). In patients with asthenospermia, the declined sperm motility was associated with decreased seminal PON-1 activity, which showed significant differences between patients with mild, moderate, and severe asthenospermia. Seminal PON-1 activity was positively correlated with the percentage of sperm viability (P<0.01), but inversely with the percentage of morphologically abnormal sperm (P<0.01). According to ROC curves, the area of seminal PON-1 activity under the curve was 0.907, showing a statistical significance (P<0.01).

CONCLUSIONThe detection of seminal PON-1 activity can provide a laboratory evidence for the diagnosis of male infertility.

Adult ; Aryldialkylphosphatase ; metabolism ; Case-Control Studies ; Humans ; Infertility, Male ; diagnosis ; metabolism ; Male ; Semen ; metabolism ; Semen Analysis ; Young Adult

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

OBJECTIVETo investigate the relationship of nitric oxide (NO) and nitric oxide synthase (NOS) with varicocele (VC) infertility.

METHODSFifty-three infertile men, 21 with varicocele and 32 with subvaricocele, were enrolled as Group 1, 29 infertile patients with oligoasthenozoospermia but without varicocele as Group 2 and 28 normal fertile controls as Group 3. The NO content and NOS activity in the seminal plasma and peripheral blood were measured by nitric acid reductase method, and the semen parameters of VC determined by computer-assisted semen analysis (CASA).

RESULTSSignificant differences were noted between Group 1 and the other two in the NO content and NOS activity in the seminal plasma (P < 0.05) but not in the peripheral blood (P > 0.05). In Group 1, the NO content and NOS activity were increased in both the seminal plasma and peripheral blood with the enhanced diameter of the varicose spermatic vein, with a significant difference only in the seminal plasma between the varicocele and subvaricocele patients (P < 0.05), and the same increase was observed with decreased sperm concentration (> or = 20 x 10(6)/ml and < or = 10 x 10(6)/ml) and motility (> or = 50% and < or = 25%), with significant differences (P < 0.05).

CONCLUSIONNO plays an important role in the VC-induced decrease of seminal quality. For the diagnosis of VC, the determination of the NO content and NOS activity in the seminal plasma is of more significance than that in the peripheral blood, and the earlier the determination, the greater its clinical value for both the diagnosis and treatment of VC.

Adult ; Humans ; Infertility, Male ; etiology ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Semen ; cytology ; metabolism ; Semen Analysis ; Sperm Count ; Varicocele ; complications ; metabolism ; Young Adult

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

OBJECTIVETo investigate the influence of varicocele (VC) on semen parameters and the concentration of inhibin B in the serum and seminal plasma of VC men.

METHODSWe collected semen and peripheral blood samples from 95 infertile VC patients and 55 normal fertile men. We performed semen routine examination by computer-assisted semen analysis and sperm morphology examination by modified Papanicolaou staining, and measured the levels of inhibin B in the peripheral blood and seminal plasma of the subjects by ELISA.

RESULTSCompared with the normal fertile controls, the infertile men with grade-I, -II and -III VC showed significantly lower percentages of morphologically normal sperm ([7.5 +/- 5.2]% vs [6.3 +/- 6.5]%, [2.6 +/- 3.0]% and [1.0 +/- 0.7]%, P < 0.05) and progressively motile sperm ([43.9 +/- 22.7]% vs [33.3 +/- 20.8]%, [28.9 +/- 19.8]% and [13.5 +/- 8.4]%, P < 0.05). The majority of the morphologically abnormal sperm were of the type of head deformity. The concentrations of inhibin B in the peripheral blood and seminal plasma were evidently lower in the infertile men with grade-I VC ([160.9 +/- 48.9] pg/ml and [208.3 +/- 28.1] pg/ml), grade-II VC ([150.6 +/- 44.7] pg/ml and [201.5 +/- 83.5] pg/ml), and grade-III VC ([132.6 +/- 41.5] pg/ml and [150.2 +/- 51.6] pg/ml) in comparison with those of the fertile control group ([201.0 +/- 38.1] pg/ml and [225.3 +/- 82.5] pg/ml).

CONCLUSIONVaricocele reduces sperm motility, increases sperm abnormality, decreases the concentration of inhibin B in the serum and seminal plasma, and consequently damages male fertility.

Adult ; Case-Control Studies ; Humans ; Infertility, Male ; physiopathology ; Inhibins ; blood ; metabolism ; Male ; Semen ; cytology ; metabolism ; Semen Analysis ; Sperm Motility ; Varicocele ; blood ; metabolism

ObjectiveTo investigate the relationship between seminal plasma zinc alpha-2 glycoprotein (ZAG) and semen quality in obese males.

METHODSThis study included 130 obese male patients with idiopathic infertility Based on the concentration of seminal plasma ZAG, we divided the patients into three tertile groups: tertile 1 (T1, 73.45－97.15 μg/ml, n = 43), T2 (97.16－115.46 μg/ml, n = 44), and T3 (115.47－220.11 μg/ml, n = 43). We measured the concentrations of seminal plasma zinc (SPZ) and ZAG of the patients by ELISA, obtained the semen parameters, and analyzed the correlation of semen quality with the levels of SPZ and ZAG and the influence of obesity on SPZ, ZAG and semen quality.

RESULTSThe mean level of seminal plasma ZAG in the 130 obese male patients was (111.29 ± 26.50) μg/ml. There were statistically significant differences in sperm concentration and total sperm count among the three tertile groups (P < 0.05). The level of seminal plasma ZAG was correlated negatively with the body mass index (BMI), waist circumference (WC), sperm concentration and sperm count (P < 0.01), that of SPZ positively with BMI and WC (P < 0.05) but negatively with semen volume and the percentage of progressively motile sperm (P < 0.05). The level of serum ZAG, however, exhibited no correlation with SPZ, seminal plasma ZAG or semen quality. Obesity was found to be associated with significantly decreased concentration of seminal plasma ZAG and percentage of progressively motile sperm but remarkably increased level of SPZ (P < 0.05).

CONCLUSIONSObesity may induce the metabolic disorder of SPZ and ZAG, change the microenvironment of seminal plasma, and consequently affect semen quality.

Body Mass Index ; Humans ; Infertility, Male ; etiology ; metabolism ; Male ; Obesity ; complications ; metabolism ; Semen ; chemistry ; Semen Analysis ; Seminal Plasma Proteins ; analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; metabolism ; Waist Circumference

OBJECTIVETo detect free testosterone (FT) in the serum and semen of patients with idiopathic oligospermia, and further analyze the relationship between FT and idiopathic oligospermia.

METHODSBlood samples were collected from the males of a normal control group (n = 44) and an idiopathic oligospermia group (n = 44) at 8:00-10:00 a.m.. Semen samples were collected from the males of a normal control group (n = 30) and an idiopathic oligospermia group (n = 37) at the same time. Sperm density was detected by routine semen analysis, and FT in the serum and semen was detected by RIA.

RESULTSThere was no significant difference in the serum concentrations of FT between the groups of normal control [(97.50 +/- 46.96) pmol/L] and idiopathic oligospermia [(94.88 +/- 42.04) pmol/L], P > 0.5. But the difference was significant in the semen concentrations of FT between the groups of normal control [(2.01 +/- 0.32) pmol/L] and idiopathic oligospermia [(0.52 +/- 0.44) pmol/L], P < 0.01.

CONCLUSIONMeasurement of semen FT concentration could early reflect the function of the testis, which contributes to the early diagnosis and treatment of idiopathic oligospermia.

Adult ; Case-Control Studies ; Humans ; Male ; Middle Aged ; Oligospermia ; blood ; metabolism ; Semen ; chemistry ; Testosterone ; blood ; metabolism

Human epididymis protein 4(HE4) is a secretory glycoprotein found in human distal epididymis epithelial cells. It is often used in the early diagnosis, efficacy evaluation and monitoring of ovarian cancer, and also has been considered as an effective serum marker for many other types of cancer. However, its function in the process of sperm maturation is not fully unknown. The maturation of sperm in epididymis is characterized by the acquisition of motility and fertilization. As a member of the whey acid protein (WAP) family, several studies proposed the importance of HE4 in the maturity of sperm in epididymis. This article reviews the effect of HE4 on spermatozoa maturation in epididymis, which provides basis for the evaluation of male reproductive ability, early detection, early diagnosis and pathogenesis of male infertility.
Epididymis/metabolism* ; Humans ; Male ; Semen ; Sperm Maturation ; Sperm Motility ; Spermatozoa/metabolism*

ObjectiveTo investigate the expression and location of IQ motif-containing G (IQCG) in the human testis, compare its expression in normal-motility sperm with that in the sperm of asthenospermia patients, and explore its possible mechanisms and its correlation with fertility.

METHODSThe expression of the IQCG gene in the human testis was detected by RT-PCR and its location in the testis and sperm was determined by immunohistochemistry and immunofluorescence staining. Semen samples were collected from normal males, patients with asthenospermia, and fertile men that succeeded in artificial insemination with donor's sperm (AID), followed by analysis of the IQCG protein expression in different groups of samples by Western blot.

RESULTSImmunohistochemistry showed that IQCG was extensively expressed in the human testis, in the spermatocytes and spermatids, specifically in the sperm tail, weakly expressed or absent in the spermatogonial stem cells, and strongly expressed in the spermatogonial cells. The expression of IQCG was significantly lower in the asthenospermia patients than in the normal males (P= 0.041). Western blot manifested that IQCG was expressed in the semen of all the three groups of subjects, with statistically significant differences between the normal men and severe asthenospermia patients (P = 0.032) as well as between the fertile males and the severe asthenospermia group (P = 0.027) .

CONCLUSIONSIQCG may act on human sperm motility and its abnormal expression possibly reduces sperm motility and fertility. An insight into its action mechanisms may shed some new light on the etiology and treatment of asthenospermia.

Asthenozoospermia ; etiology ; metabolism ; therapy ; Fertility ; Humans ; Male ; Semen ; Sperm Motility ; Spermatozoa ; Testis ; metabolism

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.
Mice ; Animals ; Humans ; Male ; Kartagener Syndrome/metabolism* ; Cilia/metabolism* ; Semen ; Genetic Testing ; RNA, Messenger ; Mutation