Actualización sobre COVID-19 e histofisiología del sistema reproductor masculino / Update on COVID-19 and histophysiology of the male reproductive system

RESUMEN: La reciente pandemia de la COVID-19 ha sacudido a la sociedad teniendo una importante repercusión en el campo de la salud y de la investigación. Dada su relevancia, se han llevado a cabo estudios sobre los efectos del SARS-CoV-2 en la fisiología humana. En concreto, sobre la posible presencia y transmisión del virus a través del sistema reproductor masculino y su posible efecto en el éxito reproductivo. Conocer si la presencia del virus altera los órganos responsables del desarrollo y maduración de las células de la serie espermatogénica podría revelarnos su implicación en la calidad seminal. Por ello, nos planteamos esta revisión, con el fin de analizar las principales evidencias científicas sobre los efectos del SARS-CoV-2 en la histofisiología del sistema reproductor masculino y sobre la capacidad fecundante de los espermatozoides.

SUMMARY: The recent COVID-19 pandemic has shaken up society, having a significant impact on the field of health and research. Given its relevance, studies have been performed on the effects of SARS-CoV-2 on human physiology. In particular, the possible presence and transmission of the virus through the male reproductive system could affect reproductive success. Knowing if the presence of the virus disrupts the organs responsible for the development and maturation of the cell lines involved in spermatogenesis could reveal its implications in sperm quality. For that reason, we proposed this review, in order to analyze the main scientific evidence on the effects of SARS-CoV-2 on the histophysiology of the male reproductive system and sperm fertilizing capacity.

Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

BACKGROUND@#The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.@*METHODS@#Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined.@*RESULTS@#Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis.@*CONCLUSION@#These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

Review of post bariatric surgery effects on common genitourinary physiology

ABSTRACT Background: Obesity is a worldwide challenging health problem. Weight loss through medical management of obesity has not always been successful, thus, giving rise to the need for surgical intervention. Bariatric surgery has been shown to be helpful for morbidly obese patients. However, studies have also shown the effect of surgery on stone formation, fertility and erectile function. This review summarizes the main findings of several studies that analyze stone formation and fertility in men as well as erectile function post bariatric surgery. The underlying pathophysiologic alterations post bariatric surgery include increased absorption of oxalate leading to hyperoxaluria, hypocitraturia and increased urinary calcium oxalate supersaturation. Contradicting data exist on the effect of bariatric surgery on fertility and erectile function. Further studies are needed to analyze the mechanisms.

Male fertility potential alteration in rheumatic diseases: a systematic review

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Hybrid Method of Transurethral Resection of Ejaculatory Ducts Using Holmium:Yttriumaluminium Garnet Laser on Complete Ejaculatory Duct Obstruction

A 32-year old single man presented with azoospermia and low semen volume which was noted one and half a year ago. Transrectal ultrasonography and seminal vesiculography were performed to evaluate ejaculatory duct obstruction, and transurethral resection of the ejaculatory duct was performed using a hybrid technique of holmium:yttriumaluminium garnet laser with monopolar transurethral resection to overcome the narrow prostatic urethra. To our knowledge, this is the first report on the successful outcome of a hybrid technique applied for transurethral resection of the ejaculatory duct.

Rapid thawing human sperm does not affect basic parameters in normozoospermic men: a double-blind prospective study

PURPOSE: To compare sperm recovery from slow versus rapid thawing technique using thirty-eight normozoospermic human sperm samples, as follows. Twenty-one samples from men taking part in routine infertility screening exams (infertile group) and seventeen from proven fertile volunteer men with at least one child (fertile group). MATERIALS AND METHODS: After analysis of motility, concentration, strict morphology and functional integrity of membranes, sperm was divided into two aliquots of 0.5 mL each and frozen in TyB-G medium. Samples were thawed at room temperature (25 ± 2º C) for 25 minutes (slow thaw) or in a water bath at 75º C for 20 seconds followed by water bath at 37º C for 3 minutes (rapid thaw). After thawing, motility, strict morphology and functional integrity of membranes were evaluated by a blinded investigator. The results were expressed as mean ± standard deviation for parametric variables and analyzed using Student's t-test. Data with unpaired non-parametric variables were expressed as median (interquartile range) and analyzed by the Mann-Whitney test. Wilcoxon test was used to analyze non-parametric paired variables. RESULTS: There was no significant difference between techniques for total and progressive motility, percentage of normal morphological forms, hypoosmotic swelling test. CONCLUSIONS: Although the rapid thawing protocol was completed in a shorter time (three minutes and 20 seconds versus 25 minutes, respectively), it wasn't harmful since both techniques showed comparable spermatozoa recovery. Additional research is needed to confirm its safety in clinical research before introducing this methodology in routine assisted reproduction.

Novel concepts in male infertility

Extraordinary advances have been achieved in the field of male infertility in the last decades. There are new concepts in sperm physiology and several modern tools for the assessment of spermatogenesis kinetics in vivo. New tests using molecular biology and DNA damage assays allow the clinician to correctly diagnose men so far classified as having idiopathic male infertility. In the field of treatment, microsurgery has increased success rates either for reconstruction of the reproductive tract or the retrieval of spermatozoa for assisted conception. Emerging evidence suggests that life-style and environmental conditions are of utmost importance in male fertility and subfertility. This review discusses several concepts that have changed over the last years, such as the duration of the spermatogenic cycle in humans, Y-chromosome infertility, the reproductive potential of non-mosaic Klinefelter syndrome men, the impact of paternal age and sperm DNA in male infertility, the role of antioxidants in the treatment of infertile men, the predictive factors and techniques for sperm retrieval in non-obstructive azoospermia, and the microsurgical treatment of clinical varicoceles. Whenever possible, levels of evidence are provided as suggested by the Oxford Center of Evidence-based Medicine.

Oxidative stress & male infertility.

The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.

Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis

Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI) technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART).

Aumento del daño en el ADN y estrés oxidativo en espermatozoides de pacientes con oligozoospermia idiopática y antecedentes de criptorquidismo / Extent of sperm DNA damage in spermatozoa from men examined for infertility. Relationship with oxidative stress

Background: Cryptorchidism and oligozoospermia are clinical conditions closely associated with impaired fertility. Oxidative stress and related sperm DNA damage have been identified as significant causes of male infertility. Aim: To determine the extent of sperm nuclear DNA damage in patients affected with idiopathic oligozoospermia or undescended testes and to examine its relationship with oxidative stress. Patients and methods: We studied 20 patients with idiopathic oligozoospermia and 18 with undescended testes (who previously underwent orchiopexy) and 25 normozoospermic healthy controls. All subjects underwent semen analysis. Sperm DNA damage was evaluated by the sperm chromatin structure assay/flow cytometry (SCSA-FCM) and by the dUTP-biotin nick end labeling (TUNEL) assay. Levels of reactive oxygen species (ROS) and total antioxidant capacity (TAC) were assessed by a chemiluminescence assay. Results: DFI (percentage of sperm with denatured DNA) values and percentage of TUNEL positive cells were significantly greater in patients with oligozoospermia (DFI: 28.8±5.6; TUNEL+: 26.9±3.0) or cryptorchidism (DFI: 26.4±10.1; TUNEL+: 29.1±3.9), compared with controls (DFI: 7.1±0.9; TUNEL+: 14.2±1.2). Similarly, both groups of patients had significantly higher (p <0.01) levels of ROS. TAC levels did not differ between control and patient groups, suggesting that the DNA damage occurs before spermiation. Conclusions: Sperm DNA damage is significantly increased in men with idiopathic oligozoospermia and in cryptorchid subjects. The finding of increased ROS levels may indicate that seminal oxidative stress may be involved in the pathogenesis of sperm DNA damage in these patients.

Current concepts and controversies in undescended testes.

Cryptorchidism, or undescended testis, is the most common genital anomaly identified at birth in males that continues to challenge the pediatric specialist. The last two decades have seen rapid improvements in understanding the complex mechanisms underlying the genesis of cryptorchidism. Yet, despite years of study, answers to questions relating to controversies surrounding undescended testes remain elusive. This article presents an overview of the controversies and current understanding of this challenging problem.

A male-sterile mutation in soybean (Glycine max) affecting chromosome arrangement in metaphase plate and cytokinesis

A spontaneous male-sterile, female-fertile mutation affecting bivalent arrangement at the metaphase plate and cytokinesis was detected in line BR98-197 of the soybean breeding program developed by Embrapa - National Soybean Research Centre. Untill diakinesis, meiosis was normal with chromosome pairing as bivalents. From this phase, in several meiocytes, bivalents were not able to organize a single metaphase plate and remained scattered in the cytoplasm in a few or several groups. In these meiocytes, chromosomes segregated in both divisions giving rise to several micronuc1ei. However, the main cause of male sterility was the absence of cytokinesis after telophase II. Instead of the typical tetrads of microspores, four nucleate coenocytic microspores were formed. In the mutant, pollen mitoses did not occur, and after engorgement by starch, pollen underwent a progressive process of degeneration

Integrins and disintegrins: the candidate molecular players in sperm-egg interaction.

Fertilization includes sperm-egg recognition, adhesion, binding, fusion and egg activation. Integrin (ITG) receptors which are adhesion molecules are expressed on mouse, hamster and human gametes and their potential ligands also have been identified. Role of ITGs during fertilization is supported by inhibition of sperm-egg adhesion and/or fusion by means of anti-ITG mAbs, Arg-Gly-Asp (RGD) or disintegrin-like peptides. This review includes the current understanding of the molecular mechanism that regulates sperm-egg interaction and implications of this knowledge for assessing the fertility potential of men and immunocontraceptive method.

Correlation between creatine kinase activity, lipid-peroxidation and water test in male infertility.

New approaches need to be pursued towards the assessment of sperm quality using biochemical markers. In order to help develop a good biochemical marker to assess sperm-membrane integrity, the enzyme creatine kinase (CK) was studied in semen of normal, oligospermic and azoospermic samples and correlated with sperm concentration, lipid-peroxidation (LP) and water test. Presence of isoforms of creatine kinase (CK-MB) was also seen. An inverse correlation was observed between CK activity and sperm concentration (p<0.001). Water test was seen to be inversely correlated with CK activity (p<0. 001). Lipid peroxidation showed positive correlation with CK activity (p<0.001). A significant correlation between loss of sperm function meditated by induction of peroxidative damage to sperm plasma membrane is indicated. Enzymes like CK can serve as good biochemical marker along with lipid peroxidation to confirm loss of sperm membrane integrity. The water test can be used as a preliminary screening test for sperm membrane integrity.

Efecto de la diabetes inducida sobre la reproducción y el desarrollo / Effect of induced diabetes upor reproduction and development

La diabetes mellitus es una enfermedad con una gran morbilidad y mortalidad, por lo que sus efectos se han estudiado en relación con los diversos órganos a los que afecta, sin ser la función reproductora la excepción. Para lograr esto, se ha recurrido a utilizar diversos animales como modelos experimentales, a los que se les induce diabetes. Se han descrito diversas sustancias para inducir la diabetes en animales, siendo la estretptozotocina (STZ) la que ha demostrado mayor eficacia. La STZ es un antibiótico producido por Streptomyces achromogenes, el cual tiene selectividad por las células beta del páncreas, destruyéndolas a través de la fragmentación del DNA. Se ha comprobado que la STZ diluida en amortiguador, estabilizada durante dos horas aproximadamente y almacenada a 6ºC, tiene una gran capacidad inductora de diabetes, sobre todo en especies como la rata, el ratón y el hamster. En ratas con diabetes inducida las alteraciones reproductivas se han asociado con alteraciones a nivel del eje hipotálamo-hipófisis-gónada, tanto por disminución de secreción de GnRH, como por deficiente secreción de LH, FSH y prolactina, así como por alteraciones a nivel gonadal y producción de hormonas esteroideas (testosterona, estrógenos y progesterona). Esto trae como consecuencia en ratas machos, la menor producción de espermatozoides, así la disminución en la movilidad de los mismos. En el caso de las hembras, las principales alteraciones son atrofia avárica, foliculogénesis anormal, insuficiencia del cuerpo lúteo, involución uterina y problemas asociados con el mantenimiento de la gestación. En diversos estudios se ha observado la prevalencia de malformaciones congénitas en los productos de ratas con diabetes inducida con STZ, siendo las más frecuetnes retraso en el desarrollo, alteraciones en el cierre del tubo neural, alteraciones cardiaca y micrognatias, entre otros

Reaçäo acrossômica na exploraçäo de infertilidade masculina em fecundaçäo in vitro / Place of acrosomal reaction in the exploration of male infertility in in vitro fertilization

O acrossoma, vesícula de origem golgiana, tem um papel essencial no desenvolvimento da fecundaçäo, tanto in vivo com in vitro. Neste artigo estudaram diferentes métodos de induçäo da reaçäo cromossômica (RA). Os indutores como o líquido folicular, a progesterona e o cálcio iônico permitem a exploraçäo da dinâmica da RA e a análise dos espermatozóides aptos a realizar esta RA. Este trabalho mostra o interesse destas exploraçöes nos casos de infertilidade masculina em Reproduçäo Assistida.

El factor masculino I. Función testicular y gametogénesis / The masculine factor: Testicular function and gametogenesis

En los últimos 15 años el estudio y tratamiento de los trastornos de la reproducción humana han avanzado notablemente en lo relativo a la infertilidad y esterilidad femeninas. Desafortunadamente no ha sucedio lo mismo en el caso del hombre, y a pesar de los esfuerzos realizados poco se ha adelantado en cuanto al diagnóstico y terapéutica del varón infértil. La gónada masculina tiene dos funciones principales: la producción de espermatozoides y por otra la síntesis y secreción de hormonas esteroides, principalmente testosterona. La regulación eficiente de la función testicular depende tanto de la secreción pulsátil precisa de las hormona gonadotróficas por la hipófisis, como de la respuesta endocrína, paracrina y autocrina concertada de las células somáticas de la gónada masculina a esta estimulación. En este trabajo se presentan los principales eventos asociados con la espermatogénesis, incluyendo tanto las interacciones entre las células somáticas del testículo, como algunas características del funcionamiento del eje hipotálamico-hipófisis- testículo, y algunos estados fisiopatológicos relacionados con la infertilidad masculina debida a causa de las denominadas "pretesticulares"

El factor masculino. II. El espaermatozoide. Estructura y funcionamiento / The masculine factor. II. The spermatozoa. Structure and functioning

En la entidad denominada ®factor masculino¼, la correlación estructural y funcional que determina la habilidad fertilizante del espermatozoide está constituida por un conjunto de aspectos celulares que deben evaluarese en el semen del varón infértil. Estructuralmente los espermatozoides están formados por la cabeza, la pieza media y el flagelo. La cabeza contiene un núcleo haploide, muy condensado, rodeado por una capa delgada de material citoplasmático, circunscrito a su vez en su parte proximal por la membrana que delimita al acrosoma. Este último organelo de características similares a un gránulo secretor, libera en forma programada las enzimas hidrolíticas que facilitan el proceso de la fertilización. En la pieza media están integradas las mitocondrias, responsables del metabolismo energético celular. El flagelo tiene la estrucutra propia de todos los cilios y flagelos, pero con características particulares debidas a la presencia de las fibras densas externas y la cubierta fibrosa. En el análisis del semen de varones infértiles las anormalidades que se presentan con mayor freucencia corresponden al número, morfología, viabilidad y la capacitación-reacción acrosomal espermática. Sin embargo, debido a la aparente etiología multi-factorial del factor masculino, actualmente solo disponemos de discretas opciones racionales para el tratamiento correspondiente. En este trabajo se discuten la morfología y ultraestructura consideradas como ®normales¼ en los epsermatozoides humanos y se describen las alteraciones más frecuentes de la misma. Asimismo, se evalúa la repercusión de las características de la movilidad y la capacitación-reacción acrosomal en la fertilidad masculina

El factor masculino. III. Importancia, diagnóstico y perspectivas / The masculine factor. III. Importancia, diagnosis and perspectives

De acuerdo con la Organización Mundial de la Salud el factor masculino está presente en el 40-50 por ciento de las parejas infértiles, de aquí la importancia en la continuidad de los estudios multidisciplinarios relacionados con los mecanismos que regulan el fenómeno reproductivo en el hombre. El análisis completo del semen o espermatobioscopia, continúa siendo prácticamente el único instrumento para el estudio del varón con trastornos en su fertilidad. Sin embargo, el principal problema para establecer un diagnóstico confiable con valor predictivo de infertilidad masculina, radica en que aún están en proceso de validación el conjunto de características morfológicas y/o funcionales del gameto masculino que determinan su habilidad fertilizante. Aún más, tampoco se ha establecido con precisión la correlación entre las características del semen y las concentraciones hormonales, bioactivas presentes en sangre periférica, con el potencial de fertilidad de un individuo. En este contexto se presentan los aspectos que se consideran más importantes en relación con la fertilidad masculina, entre otros: las principales causas de la infertilidad, el avance en el establecimiento de la correlación morfofuncional que determina la habilidad fertilizante del gameto masculino y los criterios que deben prevalecer en el laboratorio para el manejo y evaluación correcta de las muestras de semen