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1.
Pan Afr Med J ; 45: 177, 2023.
Artículo en Francés | MEDLINE | ID: mdl-37954441

RESUMEN

Introduction: in Lubumbashi, as in upscale areas where explorations of fertility are very clever, the spermogram remains the essential analysis in the diagnosis of male infertility. This is the cause of 40% of couple infertility. The spermogram is the first step in identifying seminal abnormalities. The objective of this study was to determine the epidemiological-clinical and seminal profile of the man consulting for the desire to procreate in Lubumbashi. Methods: this was a cross-sectional study. We received 202 subjects in Lubumbashi, whose spermogram was performed from August 1st, 2020 to July 31st, 2021. The semen parameters were studied and interpreted according to WHO standards (2010) with studies of factors associated with their disturbance. Bivariate and multivariate analyzes had been carried out. The statistical significance threshold was set at p < 0.05. Results: the epidemiological-clinical profile of the respondents was as follows: the most represented age group was 30 to 39 years; infertility was primary in 80.69% of cases; the duration of the desire for paternity was 2 years at most in 44.55% of cases. The sperm abnormalities found were: oligozoospermia (40.09%), azoospermia (11.38%), asthenozoospermia (18.31%) and teratozoospermia (10.39%). Oligozoospermia was significantly associated with varicocele (ORa = 10.9 [3.0-39.5]; p < 0.0001), genital infection (ORa =2.7 [1.0-7, 2]; p = 0.041) and obesity (ORa = 2.6 [1.0-7.9]; p = 0.020) while azoospermia was the cure for inguinal hernia (ORa = 4.2 [1.0-17.2]; p = 0.049) and malnutrition (ORa =6.0 [1.2-29.7]; p = 0.027). Asthenozoospermia was significantly associated with the age group of 40 to 49 years (ORa = 6.6 [1.2-37.4]; p = 0.034), tobacco (ORa =7.5 [2.7 -21.0]; p = 0.000), undernutrition (ORa = 7.7 [1.0-61.9]; p = 0.045) and overweight (ORa =3.8 [1.3-11, 5]; p=0.019). Teratozoospermia was significantly associated with smoking (ORa = 5.6 [1.8-17.7]; p = 0.003) and overweight (ORa =5.3 [1.2-23.3]; p = 0.027). Conclusion: more than half of the respondents had, of the three main fertility parameters, at least one that was disturbed. Sperm count was the most affected parameter. Alcohol, tobacco, genital infection and malnutrition were the most common risk factors for the abnormalities observed.


Asunto(s)
Astenozoospermia , Azoospermia , Infertilidad Masculina , Desnutrición , Oligospermia , Teratozoospermia , Masculino , Humanos , Adulto , Persona de Mediana Edad , Oligospermia/complicaciones , Azoospermia/complicaciones , Astenozoospermia/complicaciones , Sobrepeso/complicaciones , Teratozoospermia/complicaciones , Estudios Transversales , República Democrática del Congo/epidemiología , Semillas , Infertilidad Masculina/epidemiología , Infertilidad Masculina/etiología , Desnutrición/complicaciones
2.
Genes (Basel) ; 14(2)2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36833310

RESUMEN

Infertility is a major health problem worldwide without an effective therapy or cure. It is estimated to affect 8-12% of couples in the reproductive age group, equally affecting both genders. There is no single cause of infertility, and its knowledge is still far from complete, with about 30% of infertile couples having no cause identified (named idiopathic infertility). Among male causes of infertility, asthenozoospermia (i.e., reduced sperm motility) is one of the most observed, being estimated that more than 20% of infertile men have this condition. In recent years, many researchers have focused on possible factors leading to asthenozoospermia, revealing the existence of many cellular and molecular players. So far, more than 4000 genes are thought to be involved in sperm production and as regulators of different aspects of sperm development, maturation, and function, and all can potentially cause male infertility if mutated. In this review, we aim to give a brief overview of the typical sperm flagellum morphology and compile some of the most relevant information regarding the genetic factors involved in male infertility, with a focus on sperm immotility and on genes related to sperm flagellum development, structure, or function.


Asunto(s)
Astenozoospermia , Infertilidad Masculina , Masculino , Humanos , Femenino , Cola del Espermatozoide , Astenozoospermia/complicaciones , Astenozoospermia/genética , Semen , Motilidad Espermática , Infertilidad Masculina/genética
3.
Cell Death Dis ; 14(2): 127, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36792588

RESUMEN

The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility. Herein, we detected bi-allelic DNALI1 mutations [c.663_666del (p.Glu221fs)], in an ASZ patient, which resulted in the complete loss of the DNALI1 in the patient's sperm. We identified loss of sperm DNAH1 and DNAH7 rather than DNAH10 in both DNALI1663_666del patient and Dnali1-/- mice, demonstrating that mammalian DNALI1 is a LIC protein of a partial IDA subspecies. More importantly, we revealed that DNALI1 loss contributed to asymmetries in the most fibrous sheath (FS) of the sperm flagellum in both species. Immunoprecipitation revealed that DNALI1 might interact with the cytoplasmic dynein complex proteins in the testes. Furthermore, DNALI1 loss severely disrupted the transport and assembly of the FS proteins, especially AKAP3 and AKAP4, during flagellogenesis. Hence, DNALI1 may possess a non-classical molecular function, whereby it regulates the cytoplasmic dynein complex that assembles the flagella. We conclude that a DNALI deficiency-induced IDAs injury and an asymmetric FS-driven tail rigid structure alteration may simultaneously cause flagellum immotility. Finally, intracytoplasmic sperm injection (ICSI) can effectively resolve patient infertility. Collectively, we demonstrate that DNALI1 is a newly causative gene for AZS in both humans and mice, which possesses multiple crucial roles in modulating flagellar assembly and motility.


Asunto(s)
Astenozoospermia , Infertilidad Masculina , Animales , Humanos , Masculino , Ratones , Proteínas de Anclaje a la Quinasa A/metabolismo , Astenozoospermia/genética , Astenozoospermia/complicaciones , Astenozoospermia/metabolismo , Dineínas Axonemales/genética , Dineínas Axonemales/metabolismo , Dineínas Citoplasmáticas/metabolismo , Dineínas/genética , Dineínas/metabolismo , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Mamíferos , Mutación , Proteínas/metabolismo , Semen/metabolismo , Motilidad Espermática/genética , Cola del Espermatozoide/metabolismo
4.
Biomed Khim ; 68(3): 228-231, 2022 Jun.
Artículo en Ruso | MEDLINE | ID: mdl-35717587

RESUMEN

Although the relationship between the amount of vitamin B12 and the quality of sperm exists, but results are controversial and require several additional research. The objective of our study was to analyse the amount of vitamin B12 in the sperm samples from patients with chronic prostatitis and varicocele with accompanying asthenozoospermia, and to identify the relationship between the amount of vitamin B12 and asthenozoospermia. The research was carried out of men with chronic prostatitis and varicocele with accompanying asthenozoospermia and infertility at the age of 27±2 years. The material of the investigation was spermoplasm. A chemical microscopic examination of the ejaculate was carried out with a sperm analyzer and with the light microscopy. The amount of vitamin B12 in the spermoplasm was determined by the method of competitive ELISA. It was found that the level of vitamin B12 was 3.6 times lower in patients with chronic prostatitis III B and asthenozoospermia then in the control group. Among patients with varicocele of II and III grade and asthenozoospermia, the level of vitamin B12 was 4.4 times lower than in control group. A positive correlation relationship of average strength was revealed (r=0,683; p=0,001). Additionally, it was revealed that among patients with Chronic prostatitis III B and varicocele of II and III grades with accompanying asthenozoospermia, there was the positive correlation relationship of average strength (r=0,690; p=0,001) between the amount of vitamin B12 and sperm mobility. A decrease in vitamin B12 levels may serve as a marker of reproductive dysfunction in men.


Asunto(s)
Astenozoospermia , Prostatitis , Varicocele , Adulto , Astenozoospermia/complicaciones , Humanos , Masculino , Prostatitis/complicaciones , Motilidad Espermática , Varicocele/complicaciones , Vitamina B 12
5.
Reprod Sci ; 29(9): 2703-2705, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35606631

RESUMEN

PURPOSE: Studies pertaining to the effect of COVID-19 infection on male fertility are scarce. This case report describes a case of transient asthenozoospermia, absence of sperm motility, following a moderately severe COVID-19 infection. CASE: A couple presenting for infertility treatment due to low ovarian reserve presented for their second intrauterine insemination (IUI). Their first IUI was performed 1 month earlier when the semen parameters were normal. A couple of weeks before the second IUI, the unvaccinated 48-year-old male partner contracted COVID-19 and was admitted to the hospital for several days. He received IV Remdesivir and continuous oxygen by nasal cannula. His hospitalization did not require intubation or intensive care unit admission. He was discharged after 12 days of hospitalization without home oxygen treatment. On the day of the second IUI, the semen analysis showed a normal sperm count with 0% motility. Three months following his COVID-19 diagnosis, a repeat semen analysis showed restored normal parameters with more than 40% motility. CONCLUSION: This aim of this report is to increase awareness that moderate COVID-19 requiring hospitalization could affect, though temporarily, sperm motility and should be considered in the differential diagnosis when male infertility is encountered.


Asunto(s)
Astenozoospermia , COVID-19 , Astenozoospermia/complicaciones , Astenozoospermia/diagnóstico , COVID-19/complicaciones , Prueba de COVID-19 , Humanos , Masculino , Persona de Mediana Edad , Oxígeno , Semen , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides
6.
Reprod Biol Endocrinol ; 20(1): 41, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35232447

RESUMEN

BACKGROUND: Multiple morphological abnormalities of the sperm flagella (MMAF) is a subtype of severe asthenoteratozoospermia with poorly understood genetic etiology. SPAG6 is a core axonemal component that plays a critical role in the formation of cilia and sperm flagella. Previous studies have reported that mutations in SPAG6 cause primary ciliary dyskinesia (PCD), but the association between SPAG6 gene variants and the MMAF phenotype has not yet been described. METHODS: We performed whole-exome sequencing (WES) in two unrelated Han Chinese men with MMAF. Sanger sequencing was used to validate the candidate variants. Routine semen analysis was carried out according to the WHO guidelines (5th Edition). Sperm morphology was assessed using modified Papanicolaou staining. Scanning and transmission electron microscopy (S/TEM) was performed to observe the ultrastructural defects of the sperm flagella. Western blot analysis and immunofluorescence (IF) of spermatozoa were performed to examine the expression of SPAG6 protein. Assisted fertilization with intracytoplasmic sperm injection (ICSI) was applied. RESULTS: Two homozygous SPAG6 variants were identified by WES and Sanger validation in two patients with MMAF phenotype (F1 II-1: c.308C > A, p. A103D; F2 II-1: c. 585delA, p. K196Sfs*6). Semen analysis showed progressive rates of less than 1%, and most of the spermatozoa presented MMAF by Papanicolaou staining. TEM revealed that the overall axonemal ultrastructure was disrupted and primarily presented an abnormal "9 + 0" configuration. No other PCD-related symptoms were found on physical examination and medical consultations, as well as lung CT screening. The level of SPAG6 protein was significantly decreased in the spermatozoa, and IF analysis revealed that SPAG6 staining was extremely weak and discontinuous in the sperm flagella of the two patients. Notably, F1 II-1 and his wife conceived successfully after undergoing ICSI. CONCLUSIONS: Our research provides new evidence for a potential correlation between SPAG6 variants and the MMAF phenotype.


Asunto(s)
Astenozoospermia/genética , Proteínas de Microtúbulos/genética , Teratozoospermia/genética , Adulto , Astenozoospermia/complicaciones , Astenozoospermia/patología , China , Consanguinidad , Análisis Mutacional de ADN/métodos , Homocigoto , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/genética , Masculino , Mutación , Linaje , Fenotipo , Cola del Espermatozoide/patología , Cola del Espermatozoide/ultraestructura , Espermatozoides/anomalías , Espermatozoides/ultraestructura , Teratozoospermia/complicaciones , Teratozoospermia/patología , Secuenciación del Exoma
7.
Am J Hum Genet ; 108(8): 1466-1477, 2021 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-34237282

RESUMEN

Multiple morphological abnormalities of the sperm flagella (MMAF)-induced asthenoteratozoospermia is a common cause of male infertility. Previous studies have identified several MMAF-associated genes, highlighting the condition's genetic heterogeneity. To further define the genetic causes underlying MMAF, we performed whole-exome sequencing in a cohort of 643 Chinese MMAF-affected men. Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families. These variants were either rare or absent in public population genome databases and were predicted to be deleterious by multiple bioinformatics tools. Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs). DNAH10 encodes an axonemal IDA heavy chain component that is predominantly expressed in the testes. Immunostaining analysis indicated that DNAH10 localized to the entire sperm flagellum of control spermatozoa. In contrast, spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6. Furthermore, the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF. Altogether, our findings in humans and mice demonstrate that DNAH10 is essential for sperm flagellar assembly and that deleterious bi-allelic DNAH10 variants can cause male infertility with MMAF. These findings will provide guidance for genetic counseling and insights into the diagnosis of MMAF-associated asthenoteratozoospermia.


Asunto(s)
Astenozoospermia/complicaciones , Modelos Animales de Enfermedad , Dineínas/genética , Infertilidad Masculina/patología , Mutación , Fenotipo , Espermatozoides/patología , Alelos , Animales , Homocigoto , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/metabolismo , Masculino , Ratones , Ratones Noqueados , Espermatozoides/metabolismo , Secuenciación del Exoma
8.
Afr J Reprod Health ; 25(1): 122-128, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34077118

RESUMEN

This study evaluated pregnancy results after fresh and frozen embryo transfer in males with infertility due to non-obstructive azoospermia and oligoasthenoteratozoospermia. In this retrospective study, a total of 801 embryo transfer cycles were followed up, including 423 fresh embryo transfers and 378 frozen embryo transfers in which intracytoplasmic sperm injection (ICSI) was performed because of male infertility. This study included females aged 28-38 years without uterine, endometrial, ovarian and tubal abnormalities and with regular menstrual cycles (n=801), and males aged 28-38 years with non-obstructive azoospermia and oligoasthenoteratozoospermia. Descriptive statistical methods and the independent t-test were used in the comparison of two groups with normal distribution, the Mann-Whitney U test was used in the comparison of two groups without normal distribution, and the Chi-square test was used to compare categorical variables. There were no statistically significant differences between the fresh embryo transfer group and frozen embryo transfer group in terms of rates of pregnancy, biochemical pregnancy, clinical pregnancy, live birth rate, and abortion rate. There was no difference between fresh embryo transfer and frozen embryo transfer in terms of pregnancy results in couples with non-obstructive azoospermia and oligoasthenoteratozoospermia as male infertility factor.


Asunto(s)
Astenozoospermia/complicaciones , Azoospermia/complicaciones , Transferencia de Embrión , Infertilidad Masculina/etiología , Oligospermia/complicaciones , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas/métodos , Adulto , Femenino , Humanos , Masculino , Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos
9.
J Gynecol Obstet Hum Reprod ; 50(6): 101868, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32663655

RESUMEN

INTRODUCTION: It has been observed that there is an increased incidence of total fertilization failure (TFF) and a low fertilization rate (LFR, <25 %) during conventional in vitro fertilization (IVF) treatments involving men with poor sperm motility. These men also exhibit a high sperm DNA fragmentation index (DFI), which has adverse effects on various IVF outcomes. However, the relationship between a high DFI and an increased TFF or LFR during IVF cycles has not been elucidated. Here, we aimed to investigate the association between the sperm DFI and TFF or LFR in IVF cycles involving men with mild-to-moderate asthenozoospermia and normozoospermia. MATERIALS AND METHODS: This retrospective study included 116 men diagnosed as mild-to-moderate asthenozoospermia, and 407 men with normozoospermia. The sperm DFI was assessed using the sperm chromatin dispersion (SCD) test. RESULTS: Men in the asthenozoospermia group had a significantly higher incidence of cycles with a TFF or LFR (9.5 % vs 2.7 %, P = 0.01), and these were associated significantly with an increased DFI (P < 0.01). After adjustment for confounding factors, a TFF or LFR was to correlate significantly with the DFI (odds ratio: 1.188; 95 % confidence interval, 1.035-1.363; P = 0.014). Area under the receiver operating characteristic curve was 0.772. No similar relationships between the DFI and IVF outcomes were observed in the normozoospermia group. CONCLUSIONS: For men with mild-to-moderate asthenozoospermia, a high sperm DFI is associated with a decreased fertilization rate and an increased risk of a TFF or LFR. Additional prospectively-designed studies are warranted to confirm our results.


Asunto(s)
Astenozoospermia/complicaciones , Cromatina/patología , Fragmentación del ADN , Fertilización In Vitro , Espermatozoides/patología , Adulto , Técnicas Genéticas , Humanos , Masculino , Microscopía , Estudios Retrospectivos
10.
Arch Ital Urol Androl ; 92(4)2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33348969

RESUMEN

INTRODUCTION: In comparison to its clinical analogue, the subclinical varicocele represents a questionable entity and specific guidelines for the optimal management are lacking. In our previous study of patients with subclinical varicocele, we showed that bilateral condition is associated with risk of dyspermia. In the present study, we evaluated the risk of deterioration of semen quality in men with bilateral disease and impaired motility according to WHO criteria. MATERIALS AND METHODS: Men with bilateral subclinical varicocele, not desiring fatherhood at the time of presentation, were included in study. During initial evaluation, the number of Total Motile Sperm Count (TMSC) was calculated and the patients' age, total testicular volume (TTV), maximum venous size and mean resistive index (RI) of the intratesticular arteries were recorded. We classified the participants in five classes according to the TMSC reading: class A-: TMSC < 5 x 106, class A: TMSC between 5-10 x 106, class B: TMSC between 10-15 x 106, class C: TMSC between 15-20 x 106, and class D: TMSC > 20 x 106 per ejaculate. The participants were seen after 6 months for a repeat spermiogram and physical examination. If clinical varicocele was diagnosed or a new abnormality in the spermiogram was noted, the participants were excluded from the study. The remaining patients were allocated to two groups according to the repeat TMSC reading: patients sub-classified into a lower class (group 1), and patients remaining at the same class (group 2). A comparative analysis was performed between two groups. RESULTS: Nineteen men were included. Nine patients were subclassified (group 1). Three patients moved to A- class (< 5 x 106). Ten patients remained in the same class having no deterioration (group 2). Comparing the two groups, no statistically significant difference was recognized for age, TTV, maximum venous size on both sides, and mean RI (p > 0.05). However, the initial reading for TMSC was 14.57 x 106 in group 1, and 22.84 x 106 in group 2, respectively. This difference was statistically significant (p < 0.05). Additionally, in a paired analysis there was a significant difference in TMSC after 6 months (p < 0.05), too. Summary Conclusions: Young men with bilateral varicocele and asthenospermia seem to be at risk of deterioration in their semen quality after a follow-up of 6 months. The measurement of TMSC can unmask patients at risk, whereas men with the lowest readings seem to be at highest risk for deterioration. The possibility of a worsening sperm quality should be considered in the appropriate clinical context.


Asunto(s)
Astenozoospermia/diagnóstico , Recuento de Espermatozoides , Motilidad Espermática , Varicocele/diagnóstico , Adulto , Astenozoospermia/clasificación , Astenozoospermia/complicaciones , Humanos , Masculino , Medición de Riesgo , Varicocele/clasificación , Varicocele/complicaciones , Varicocele/patología
11.
Clin Genet ; 98(4): 396-401, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32681648

RESUMEN

Asthenozoospermia is a common cause of male infertility associated with the reduced motility and/or abnormal morphology of spermatozoa, although its etiology remains incompletely understood. Multiple morphological abnormalities of the sperm flagella (MMAF) is one of the main causes of asthenozoospermia. However, the MMAF-associated genes identified to date cannot explain all the human MMAF cases. Herein, a loss-of-function mutation of DNAH8 was identified in an asthenozoospermia patient with MMAF. Moreover, the negative effect of this mutation on DNAH8 expression was confirmed by immunofluorescence staining and western blotting. Remarkably, it is the first time that DNAH8 is suggested to be associated with human MMAF. Our findings provide strong evidence that a loss-of-function mutation in DNAH8 can cause male infertility with MMAF and that DNAH8 is essential for sperm flagellar formation.


Asunto(s)
Anomalías Múltiples/genética , Astenozoospermia/genética , Dineínas/genética , Infertilidad Masculina/genética , Anomalías Múltiples/patología , Adulto , Astenozoospermia/complicaciones , Astenozoospermia/patología , Exoma/genética , Homocigoto , Humanos , Infertilidad Masculina/patología , Mutación con Pérdida de Función/genética , Masculino , Análisis de Semen , Motilidad Espermática/genética , Cola del Espermatozoide/metabolismo , Cola del Espermatozoide/patología , Secuenciación del Exoma
12.
Actas Urol Esp (Engl Ed) ; 44(5): 281-288, 2020 Jun.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32284159

RESUMEN

Male infertility accounts for 50% of the causes of infertile couples, being more than 30% of unknown etiology. In these cases, empiric treatment can be an option prior to the application of assisted reproduction techniques. Empiric treatment can be categorized as hormonal, such as gonadotropins, antiestrogens and aromatase inhibitors, and antioxidant, with vitamins, trace elements and carnitine, among others. Although scientifically acceptable evidence is limited due to the absence of large randomized and controlled clinical trials, recent systematic reviews and meta-analyses show that treatment with gonadotropins, antiestrogens and antioxidants increases pregnancy and live birth rates and improves seminal parameters. Empiric medical treatment for idiopathic infertility can be considered in specific cases in order to improve semen quality and spontaneous fertility.


Asunto(s)
Astenozoospermia/tratamiento farmacológico , Oligospermia/tratamiento farmacológico , Algoritmos , Astenozoospermia/complicaciones , Humanos , Masculino , Oligospermia/complicaciones
14.
Am J Hum Genet ; 105(1): 198-212, 2019 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-31178125

RESUMEN

Motile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (γ-type: DNAH5 and DNAH8 and ß-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with α-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa.


Asunto(s)
Astenozoospermia/complicaciones , Dineínas Axonemales/genética , Infertilidad Masculina/etiología , Mutación , Espermatozoides/patología , Adulto , Humanos , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Masculino , Linaje , Fenotipo , Espermatozoides/metabolismo
15.
Andrology ; 7(4): 454-462, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30924599

RESUMEN

BACKGROUND: Testicular cancer (TC) is the most common cancer diagnosed in men of reproductive age group. Sperm banking is recommended in these patients prior to cancer treatment. There is no literature describing the proteins dysregulated in the spermatozoa of TC patients with poor motility. OBJECTIVE: The primary objective of this study was to compare the differences in the sperm proteome of normozoospermic (motility > 40%) and asthenozoospermic (motility < 40%) TC patients who had cryopreserved semen samples before initiating cancer therapy. MATERIALS AND METHODS: Pooled sperm samples from healthy fertile men (n = 8), normozoospermic (n = 20), and asthenozoospermic (n = 11) TC patients were used for quantitative global proteomic profiling by liquid chromatography-tandem mass spectrometry (LC-MS). The functional bioinformatic analysis was done by ingenuity pathway analysis software. Key differentially expressed proteins (DEPs) associated with binding of zona pellucida (CCT3), mitochondrial dysfunction (ATP5A1 and UQCRC2), sperm motility (ATP1A4), and an exosomal protein involved in the metabolic process of the spermatozoa (MMP9) were validated using Western blot analysis by comparing normozoospermic (n = 10) with asthenozoospermic (n = 10) TC patients. Statistical analysis was conducted using Mann-Whitney test. RESULTS: A total of 813 and 957 proteins were detected in spermatozoa of normozoospermic and asthenozoospermic TC patients, respectively. On the other hand, 1139 proteins were detected in the spermatozoa of healthy fertile men. 198 proteins were identified as DEPs between TC patients with normal and abnormal semen parameters. Validation of DEPs revealed downregulation of key proteins (CCT3, ATP1A4, ATP5A1, and UQCRC2) implicated in the reproductive function in asthenozoospermic TC patients. DISCUSSION: DEPs involved in the reproductive function pathways suggest defective spermatogenesis and maturation process in asthenozoospermic TC patients. Furthermore, dysfunctional exosomal pathway may be a possible cause of infertility in TC patients. CONCLUSION: The proteins associated with sperm function and fertilization process are compromised in TC patients irrespective of their semen parameters.


Asunto(s)
Astenozoospermia/metabolismo , Neoplasias de Células Germinales y Embrionarias/metabolismo , Proteoma , Espermatozoides/metabolismo , Neoplasias Testiculares/metabolismo , Astenozoospermia/complicaciones , Estudios de Casos y Controles , Perfilación de la Expresión Génica , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/complicaciones , Proteómica , Motilidad Espermática , Neoplasias Testiculares/complicaciones
16.
Andrologia ; 50(3)2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29315686

RESUMEN

Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.


Asunto(s)
Antioxidantes/uso terapéutico , Astenozoospermia/tratamiento farmacológico , Varicocele/tratamiento farmacológico , Adolescente , Adulto , Antioxidantes/farmacología , Astenozoospermia/complicaciones , Suplementos Dietéticos , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Resultado del Tratamiento , Varicocele/complicaciones , Adulto Joven
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(10): 1228-1231, 2017 Oct 28.
Artículo en Chino | MEDLINE | ID: mdl-29093258

RESUMEN

To investigate the clinic value of microsurgical shunt for the treatment of varicocele combined with asthenspermia, the clinical data and therapeutic method for 3 patients, who conducted the microscope spermatic vein high ligation combined with superficial epigastric vein flow, were retrospectively analyzed. No postoperative complications were found, and the original symptoms and signs were disappeared. All patients were conducted scrotal ultrasound and semen routine after 3 months, and all indexes, including maximum internal diameter of the cord vein (erect position), sperm density, sperm survival rate, sperm deformity rate and sperm forward movement rate, were gradually improved. Consequently, high ligation of spermatic vein combined with vascular bypass surgery under the microscope can block the countercurrent venous blood and establish a new return channel to the testis. Meanwhile, it can also protect the testicular artery and lymph-vessel. It is worth to be spread for the treatment of varicocele combined with asthenospermia.


Asunto(s)
Astenozoospermia/cirugía , Microcirugia , Cordón Espermático/irrigación sanguínea , Varicocele/cirugía , Venas/cirugía , Anastomosis Quirúrgica/métodos , Astenozoospermia/complicaciones , Humanos , Ligadura , Masculino , Estudios Retrospectivos , Testículo/irrigación sanguínea , Varicocele/complicaciones
18.
Andrologia ; 49(3)2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27362525

RESUMEN

Asthenozoospermia is an important cause of male infertility. The mutations in sperm mitochondrial DNA (mtDNA) result in either functionless or malfunctioning some proteins, subsequently affecting sperm motility leading to asthenozoospermia. The purpose of this study was to investigate sperm mtDNA 4,977-bp deletion in infertile men with low sperm motility/immotile spermatozoa compared to healthy subjects with high sperm motility. Semen samples of 256 asthenozoospermic infertiles and 200 controls from northern Iran were collected. After extraction of spermatozoa total DNA, Gap-polymerase chain reaction (Gap-PCR) was performed. The deletion was observed in 85.93% of patients with asthenozoospermia compared with 14% in controls [OR = 37.5397, 95% confidence interval = 12.937-108.9276, p < .0001]. It is concluded that there is a strong association between sperm mtDNA 4,977-bp deletion and asthenozoospermia-induced infertility in the population examined. Large-scale mtDNA deletions in spermatozoa may induce bioenergetic disorders. Nevertheless, to validate our results broader research may be needed.


Asunto(s)
Astenozoospermia/genética , ADN Mitocondrial/genética , Eliminación de Secuencia , Motilidad Espermática/genética , Espermatozoides/patología , Astenozoospermia/complicaciones , Secuencia de Bases/genética , Estudios de Casos y Controles , Humanos , Irán , Masculino , Reacción en Cadena de la Polimerasa
19.
Zhonghua Nan Ke Xue ; 23(5): 473-476, 2017 May.
Artículo en Chino | MEDLINE | ID: mdl-29717843

RESUMEN

Oligoasthenozoospermia, teratozoospermia or low sperm motility is the main cause of male infertility. Low sperm motility can be induced by abnormalities of the sperm tail structure and sperm function. The outer dense fiber protein 2 (ODF2) is a protein fiber maintaining cytoskeleton, as a major component of the mammalian sperm tail and centrosome, and its abnormality is closely related to asthenospermia. Recent studies indicate that ODF2 includes many proteins of the same name and homologous splices located in the sperm centrosomes and spindles of cleaved-embryos, necessary for animal ciliogenesis and associated with sperm capacitation. The features of ODF2 indicate that it is not a single-structural protein. This paper reviews the known functions of ODF2, paving a ground for further studies of the relationship between the ODF2 protein and fertilization.


Asunto(s)
Proteínas de Choque Térmico/fisiología , Espermatozoides/fisiología , Animales , Astenozoospermia/complicaciones , Azoospermia/complicaciones , Centrosoma/química , Citoesqueleto/química , Humanos , Infertilidad Masculina/etiología , Masculino , Motilidad Espermática/fisiología , Cola del Espermatozoide
20.
Andrology ; 4(5): 816-24, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27218783

RESUMEN

One of the main pathogeneses of varicocoele and infertility is oxidative stress (OS), nevertheless, the oxidative damaged DNA in infertile patients with varicocoele remains poorly clarified. The objective of this study was to comprehensively investigate whether sperm DNA damage and OS injury were related with different issues of varicocoele. According to the varicocoele practice guidelines, surgical treatment was not indicated in the infertile patients with subclinical (SubVc, n = 15) and normozoospermic clinical varicocoele (NCVc, n = 22), the infertile astheno/oligozoospermic patients with clinical varicocoele (AOCVc, n = 51) would receive microsurgerical varicocoelectomy. Normozoospermic healthy donors with proven fertility (n = 25) were recruited as controls. Thiobarbituric acid and sperm chromatin structure assay (SCSA) methods were preformed to analyze seminal lipid peroxidation product malondialdehyde (MDA) and sperm DNA fragmentation index (DFI). We found that AOCVc and NCVc, except SubVc, could significantly elevate sperm DFI and seminal MDA levels. Varicocoelectomy could substantially improve semen parameters, and reduce sperm DFI and seminal MDA levels in the AOCVc patients. However, the non-operative NCVc patients would possibly suffer a severe deterioration of semen parameters accompanied by aberrantly higher levels of sperm DFI and seminal MDA, whereas no differences occurred in the non-operative SubVc patients. Sperm DFI level in the pregnant group was much lower compared to the non-pregnant group (AOCVc, p < 0.01; NCVc, p < 0.05) with the best cutoff value of 19.73%, while no differences in seminal MDA (p > 0.05) could be observed. Finally, a strong positive correlation was found between sperm DFI and seminal MDA (Rs = 0.504, p < 0.01), and they were also closely correlated with crucial semen parameters except normal morphology. Therefore, sperm DNA damage in clinical varicocoele, but not in SubVc, might be associated with the role of seminal reactive oxygen species (ROS) in mediating such damage. Varicocoelectomy could be beneficial for reducing OS injury and sperm DFI, and males with low sperm fragmented-DNA level had more opportunities to become pregnant.


Asunto(s)
Daño del ADN/fisiología , Infertilidad Masculina/metabolismo , Estrés Oxidativo/fisiología , Espermatozoides/metabolismo , Varicocele/metabolismo , Adulto , Astenozoospermia/complicaciones , Astenozoospermia/metabolismo , Fragmentación del ADN , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/cirugía , Masculino , Malondialdehído/metabolismo , Oligospermia/complicaciones , Oligospermia/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Recuento de Espermatozoides , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos Masculinos , Varicocele/complicaciones , Varicocele/cirugía
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