Genetic pathogenesis of acephalic spermatozoa syndrome: past, present, and future / 亚洲男科学杂志(英文版)

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.

Azoospermia y fertilización asistida: rol de la histología testicular en el éxito de icsi / Azoospermia and assisted reproduction: role of testicular histology in the success of ICSI

Introducción: La infertilidad masculina afecta aproximadamente al 7por ciento de los hombres, presentándose hasta el 15 por ciento de ellos con azoospermia. El conocimiento del tipo de azoospermia (obstructiva o no obstructiva) y la localización de la falla (pre-testicular, testicular o post-testicular) es vital para conocer el pronóstico de fertilidad de la pareja y plantear un plan terapéutico adecuado. Actualmente, la extracción de espermatozoides desde epidídimo o testículo de pacientes azoospérmicos, y la posterior inyección intracitoplásmática de éstos (ICSI, por sus siglas en inglés) ha permitido obtener embriones viables para su posterior transferencia. Materiales y métodos: Estudio descriptivo retrospectivo de 42 parejas infértiles con diagnóstico de azoospermia; que se sometieron a biopsia testicular, ICSI y posterior transferencia de embriones, entre los años 2004 y 2012. Se lleva a cabo un análisis de la edad de los pacientes, resultados de la histopatología testicular y su asociación con los resultados de la fertilización asistida. Resultados: 42 pacientes azoospérmicos se sometieron a biopsia testicular y extracción de espermatozoides en el mismo acto quirúrgico. La edad promedio de los pacientes fue de 36 años para los hombres y 32 años para las mujeres. En el análisis histológico de los tejidos testiculares, el 31por ciento de los pacientes presentaban espermatogénesis conservada (EC), el 35.7 por ciento atrofia mixta (AM), el 14.3 por ciento hipoespermatogénesis (HE), el 14.3 por ciento detención de la maduración (DM) y un 4.8 por ciento presentaba otras histologías. Lograron embarazo clínico 14 de 42 parejas (33,3 por ciento), siendo la tasa de embarazo específica por patología de 38,5 por ciento para EC, 26.7 por ciento para AM, 50 por ciento para HE, 16,7 por ciento para DM y 50 por ciento para las otras histologías. 12 de las 42 parejas realizaron más de un ciclo de transferencias...

Introduction: Male infertility affects approximately 7percent of men, presenting up to 15 percent with azoospermia. Knowing the type of azoospermia (obstructive or non-obstructive) and the location of the problem (pre-testicular, testicular and post-testicular) is vital to recognize the fertility prognosis of the couple and present a proper treatment plan. Currently, the extraction of sperm from epididymis or testis of azoospermic patients, and subsequent intracytoplasmic sperm injection (ICSI) has yielded viable embryos for transfer. Materials and Methods: Retrospective study of 42 infertile couples diagnosed with azoospermia, who underwent testicular biopsy, ICSI and subsequent embryo transfer, between 2004 and 2012. We performed an analysis of the patients’ age, testicular histopathology results and their association with assisted fertilization outcome. Results: 42 azoospermic patients underwent testicular biopsy and sperm extraction in the same surgery. The average age of patients was 36 years for men and 32 years for women. Histologic analysis of testicular tissue showed that 31 percent of patients had normal spermatogenesis (NS), 35.7 percent mixed atrophy (MA), 14.3 percent hypospermatogenesis (HS), 14.3 percent maturation arrest (MTA) and 4.8 percent had other histologies. 14 of 42 couples achieved clinical pregnancy (33.3 percent), with a specific pregnancy rate of 38.5 percent for NS, 26.7 percent for MA, 50 percent for HS, 16.7 percent for MTA and 50 percent for other histologies. 12 of 42 couples underwent more than one transfer cycle. Conclusions: The use of ICSI is a suitable alternative for infertile couples with severe male factor. The results of this technique are favorable for most histologies. Patients with MA exhibit sertoli solo syndrome and / or tubular sclerosis foci associated to regions with normal spermatogenesis, enabling the sperm extraction for ICSI.

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E

OBJECTIVE: The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. MATERIALS AND METHODS: The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. RESULTS: There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. CONCLUSION: Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

Citogenética de casais inférteis / Cytogenetic of infertile couples

Introdução: A infertilidade é a ausência de gravidez, por um ano ou mais, em um casal jovem e saudável, com vida sexual ativa, sem o uso de medidas anticonceptivas. Aberrações cromossômicas podem explicar a infertilidade ou recorrência de perda gestacional. Homens e mulheres inférteis têm maiores riscos de serem portadores de alguma anomalia cromossômica. A detecção dessa anomalia é de fundamental importância para o diagnóstico da infertilidade, o aconselhamento genético, o tratamento,quando possível, e os cuidados adequados na gestação. Objetivos: Analisar citogeneticamente indivíduoscom anomalias na gametogênese masculina ou feminina e casais que relataram abortos espontâneos, caracterizar o tipo de aberrações cromossômicas encontradas orientaro casal para aconselhamento genético antes da decisão reprodutiva e antes da inclusão do mesmo em algum procedimento de reprodução assistida.Metodologia: Os indivíduos foram selecionados nos Ambulatórios de Genética e de Infertilidade do HU-UFSC. A análise citogenética foi obtida pela cultura de linfócitos do sangue periférico, sendo realizadas técnicasde banda G e banda C. Resultados: Foram estudados: seis casais comhistória de abortos espontâneos, uma paciente com amenorréia secundária, e um paciente com oligospermia. Foram encontradas aberrações cromossômicas em duas mulheres, uma com a translocação Robertsoniana (14;15)e outra com translocação envolvendo a região distal de dois cromossomos X.Conclusões: O estudo confirmou a importância de exames citogenéticos em mulheres com amenorréia secundária e em casais com história de abortos de repetição.

Background: Infertility is the absence of pregnancy during one year or more in a young and healthy couple, with an active sexual life and without the use of contraceptive. Chromosomal abnormalities can explainthe infertility or miscarriage, therefore infertile male and a female have an increased risk to carry a chromosomal abnormality. Detection of such an abnormality is of fundamental importance for the diagnosis of infertility, the genetic counseling, a possible treatment, and an appropriate care during pregnancy. Methodology: The patients were selected from the Outpatient Genetic and Infertility at HU-UFSC. The cytogenetic analysis was carried out on a lymphocytes culture of peripheral blood with GTG and CBG banding. Results: Were studied: six couples who had at least two or more spontaneous abortions, one woman with secondary amenorrhea, and one man with oligospermia. Chromosomal abnormalities were detected in two women. One with a Robertsonian translocation (14;15) and one with a translocation involving the distal region of two X chromosomes. Conclusions: The study demonstrated the importance of the cytogenetic studies in woman with secondary amenorrhea and in couples with repeated abortions.

Isolation of arcanobacterium haemolyticum in semen of an infertile patient

This is the report of a genital tract infection caused by Arcanobacterium haemolyticum in an infertile man from Venezuela. This 29 year-old patient was evaluated for primary infertility, without symptoms of seminal infection. Laboratory analysis showed leukocytospermia, low sperm count, motility and vitality, without abnormalities in hormonal profile. Sperm culture was positive for A. haemolyticum. After erythromycin therapy an improvement in some sperm parameters was observed. A. haemolyticum could be considered as a cause for silent seminal infection

Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology.

Numerous factors influence male fertility. Among these factors is oxidative stress (OS), which has elicited an enormous interest in researchers in recent period. Reactive oxygen species (ROS) are continuously produced by various metabolic and physiologic processes. OS occurs when the delicate balance between the production of ROS and the inherent antioxidant capacity of the organism is distorted. Spermatozoa are particularly sensitive to ROS as their plasma membrane contains polyunsaturated fatty acids (PUFA), which oxidizes easily. They also lack cytoplasm to generate a robust preventive and repair mechanism against ROS. The transition metal ions that are found in the body have a catalytic effect in the generation of ROS. Lifestyle behaviours such as smoking and alcohol use and environmental pollution further enhance the generation of ROS and thus, cause destructive effects on various cellular organelles like mitochondria, sperm DNA etc. This article analyzes the detrimental effects of OS on male fertility, measurement of OS and effective ways to decrease or eliminate them completely. We have also provided information on oxidative stress in other systems of the body, which may be applied to future research in the field of reproductive biology.

Changes in crossover distribution along a quadrivalent in aman carrier of a reciprocal translocation t(11; 14)

A testicu1ar biopsy from an infertile man carrying a heterozygous chromosome translocation t(ll; 14) was studied with synaptonemal complex analysis and immunolocalization of the protein MLH 1 for crossover detection. A full blockage of spermatogenesis at the spermatocyte stage was related to the presence of the translocation quadrivalents at pachytene. Only 2% of the quadrivalents showed full synapsis. Most of the spermatocytes showed asynaptic free ends that frequently mingled with the XY pair. The average number of crossovers per cell was diminished from a mean of 52.7 in controls to a mean of 48 in the patient. The difference between the number of crossovers in the quadrivalent and the normal bivalents was highly significant. The distribution of crossovers over the segment of the quadrivalent corresponding to bivalent #14 was also very different from that ofthe control. It is concluded that in this translocation, the pattern of crossovers is changed, mainly due to a synaptic hindrance in the quadrivalent, and that the spermatogenesis arrest is mainly due to the quadrivalents that interact with the XY pair

Study of semen analysis and testicular biopsy in infertile male.

A study of semen analysis and testicular biopsy was done in 50 infertile males. Semen analysis and testicular biopsy form important screening tools. Commonest age group affected was 21-40 years with sterility of 2-6 years duration. Smoking or tobacco chewing for longer periods may change semen quality. On semen analysis, 52 percent cases had azoospermia, 46 percent cases had oligospermia and 02 percent cases had normal count. Among oligospermics and normospermics, majority had more than 50 percent motility. Conditions like varicocele, undescended testis, inflammation can lead to hypospermatogenesis; the lesion is most common with 26 percent incidence. Though the specific reason of sertoli cell only is not known, it is also common with 26 percent incidence. Second most common finding was atrophy with 18 percent incidence, which may be acquired due to history of trauma, exposure to high temperature, habits of tobacco chewing and/or smoking or inflammatory conditions.

Testicular biopsy in infertility.

Eighty-eight infertile couples attended the infertility clinic. Semen analysis was abnormal in 64 cases. The cases were divided into 3 groups according to sperm count:Group I (count zero), group II (count < 20 million/ml) and group III (20-50 million/ml). The morphology of testicular biopsy categorised into 5 groups were normal--10(15.63%), hypospermatogenesis--42(65.63%), the Sertoli cell only syndrome--2(3.13%), maturation arrest--2(3.13%) and tubular hyalinization--8(12.50%). Quantitative analysis of biopsies was done using mean Johnson score(MJS) and Silber score(SS). The morphology in any single section was not uniform but of mixed type. Normal spermatogenesis in azoospermics indicated bilateral ductal obstruction. As compared to MJS, SS showed a more direct correlation between number of mature spermatids per tubular cross section and sperm count in unobstructed cases.

Ultra-sonografia transretal no diagnóstico da obstruçäo ejaculatória em pacientes inférteis / Transrectal ultrasonography in the diagnosis of ejaculatory obstruction in infertile patients

A ultrasonografia transretal de próstata realizada em 47 pacientes inférteis foi anormal em 19 (40,45 por cento). Os achados foram anormais em 5 (55,5 por cento) de 9 pacientes azoospérmicos, em 6 (42,8 por cento) de 14 oligozoospérmicos e em 8 (33 por cento) de 24 normozoospérmicos. Näo havia diferença estatística significativa entre os volumes seminais dos pacientes com e sem anormalidades ultra-sonográficas. Cistos pélvicos únicos foram encontrados em 11 pacientes e associados a outras patologias em 2 outros; em 4 casos existiam apenas vesículas seminais anormais e os 2 últimos pacientes tinham somente anormalidades em dutos ejaculatórios. Conclui-se que a possibilidade de achados sujestivos de obstruçäo ejaculatória pelo exame ultra-sonográfico é mais esperada entre os azoospérmicos com volumes seminais baixos ou normais baixos, que entre os oligos e normozoospérmicos com essas mesmas características seminais

Improvement of semen quality in infected asymptomatic infertile male after bacteriological cure

Bacteriological etiology was investigated in 29 infected asymptomatic infertile males. The localization of the infection and the effect of a long term antibiotic therapy on semen parameters were evaluated. The most frequent etiological agent isolated was Enterococcus faecalis. Positive bacteriological culture was obtained in prostatic fluid in 16 patients and in semen in 13. Bacteriological cure was achieved in 24 cases and it was associated with improved seminal parameters: sperm concentration, motility, viability and total motile sperm per ejaculate. In 5 patients without bacteriological cure there was no change in semen analysis after antibiotic therapy. In 45 percent of the infected patients there were less than 0.5 x 10(6)/ml seminal polymorphonuclear leukocytes. In view of these findings granulocyte concentration seems to be a poor marker to predict infection.

Impacto das técnicas de reproduçäo assiatida no tratamento da infertilidade masculina

Resumo: No período de 1990 a 1994, 331 pacientes do sexo masculinocom infertilidade primária foram tratados no ambulatório da Disciplina de Urologia da Faculdade de Ciências Médicas da UNICAMP. O tratamento compreendeu uma fase inicial, denominada convencional, que incluiu o tratamento clínico (varicocelectomia). Os pacientes que näo engravidaram nesta fase forama seguir encaminhados para tratamento através de reproduçäo assistida. O tratamento convencional incluiu 258 pacientes (77,95 por cento) que receberam tratamento clínico do uso de citrato de clomifeno (50 mg ao dia por via oral) ou administraçäo de gonadrofina coriônica humana (2000 UI por via intramuscular por semana) associada à gonadotrofina da menopausa (1000 UI por via intrauscular por semana) e acompanhados por 12 meses. Ao término deste período, quatro pacientes apresentavam gravidez (1,55 por cento). Os outros 73 pacientes (22,05 por cento) receberam tratamento cirúrgico (varicocelectomia) e clínico por apresentarem varicocele uni ou bilateral ao exame físico especial. Após seguimento de 18 meses, 10 pacientes apresentaram gestaçäo (13,70 por cento). O resultado geral do tratamento convencional foi de 4,23 por cento. Dentre os 317 casais que näo apresentaram gestaçäo, 63 foram tratados por reproduçäo assistida.

Testicular biopsy in male infertility.

A total of 134 testicular biopsies from infertile men were studied. The potentially treatable causes of infertility viz. Normal spermatogenesis with post-testicular obstruction, maturation arrest and hypospermatogenesis together constituted about 54 percent of all cases. The incurable causes viz., germ cell aplasia, tubular fibrosis and Klinefelter's syndrome together constituted about 42 percent of all cases. Testicular biopsy in male infertility is a very useful procedure since it gives a lot of information on the diagnosis and helps in planning treatment.

Bilateral testicular biopsy--is it necessary?

Bilateral testicular biopsies from 202 infertile males were examined to ascertain the differences in the degree of damage to the germinal epithelium on both sides. Depending on the histologic changes, the biopsies were divided into six groups. A significant difference in the morphology on both sides was seen only in 3% cases. The left and the right testes were equally damaged in cases with similar morphology.

Scanning electron microscopy in the assessment of sperm morphology.

The advantages of using scanning electron microscope (SEM) vis-a-vis light microscope (LM) to assess sperm morphology was studied. The semen samples obtained from 15 fertile (group I) and 25 infertile (group II) men were processed by routine procedures for LM and SEM. The usually described sperm abnormalities were identifiable with greater resolution. Sperm abnormalities were significantly more in group II, as compared with group I (P less than 0.001) by both methods. Abnormalities of different regions, like thinning of midpiece, were scored higher in SEM than in LM. The abnormality of aggregation or retraction of mitochondrial sheath was clearly visible under SEM and missed by LM. Apart from detection of certain subtle abnormalities, SEM has advantages of rapid screening, accurate quantitation directly from the screen, zooming to higher magnification and automation.

Variables bioquimicas relacionadas con la motividad y vitalidad espermatica masculina / Variable biochemicals to relates with the motility and spermatic vitality in the sterility masculinity

Uno de los aspectos mas enganosos de la esterilidad e infertilidad masculina es la ausencia de caracteristicas clinicas evidentes del estado de salud y fisiopatologia del testiculo, por lo que es muy importante realizar un examen minucioso del liquido seminal. En este trabajo, se determinaron 174 examenes seminologicos en pacientes con sospecha de infertilidad y esterilidad, cuyas edades fructuan entre 19 y 50 anos. El grupo de pacientes con astenospernia leve (32 %) presento vitalidad mayor de 80 %, sin embargo el 52 y el 71% de estos pacientes reportaron valores disminuidos o aumentados de los niveles de fructuosa y acido citrico respectivamente. Asimismo los pacientes catalogados con necrospernia minima, moderada severa y muy severa presentaron valores muy aumentados y disminuidos de los niveles de fructuosa y acido citrico.