BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function.
OBJECTIVE: To investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters.
METHODS: Prospective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined.
RESULTS: 11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics.
CONCLUSIONS: 11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.

Orexins A (OXA) and B (OXB) and their specific receptors, receptor 1 (OX1R) and 2 (OX2R) for orexins, are hypothalamic peptides involved in orchestrating several functions in the central nervous system and peripheral organs, including sleep, excitement, nutrition, reward, circadian rhythm, anxiety, cognition, and reproduction. The aim of this narrative review is, in particular, to speculate the role of orexins in the male genital tract of animal species and human beings. The experimental evidence collected in recent years assumed that in the testes of the animal species here described, orexins are directly involved in steroidogenesis and spermatogenesis regulation. In the epididymis, these peptides are locally synthesized, thus suggesting their role governing the fertilizing capability of the immature male gamete. In addition to playing a physiological role, orexins are involved in numerous inflammatory and/or neoplastic pathologies too. The expression of the orexinergic system in prostate cancer suggests that they might play a potential therapeutic function. Overall, the future directions of this literature review allow us to hypothesize a role of the orexinergic complex not only as a marker for the diagnosis of certain tumors affecting the male genital tract but also for the treatment of hypo/infertility condition.

Many viruses infect the male genital tract with harmful consequences at individual and population levels. In fact, viral infections may induce damage to different organs of the male genital tract (MGT), therefore compromising male fertility. The oxidative stress, induced during viral-mediated local and systemic inflammation, is responsible for testicular damage, compromising germinal and endocrine cell functions. A reduction in sperm count, motility, number of normal sperm and an increase in DNA fragmentation are all common findings in the course of viral infections that, however, generally regress after infection clearance. In some cases, however, viral shedding persists for a long time leading to unexpected sexual transmission, even after the disappearance of the viral load from the blood.The recent outbreak of Zika and Ebola Virus evidenced how the MGT could represent a reservoir of dangerous emergent viruses and how new modalities of surveillance of survivors are strongly needed to limit viral transmission among the general population.Here we reviewed the evidence concerning the presence of relevant viruses, including emergent and re-emergent, on the male genital tract, their route of entry, their adverse effects on male fertility and the pattern of viral shedding in the semen.We also described laboratory strategies to reduce the risk of horizontal or vertical cross-infection in serodiscordant couples undergoing assisted reproductive technologies.
RéSUMé: De nombreux virus infectent l’appareil génital masculin avec des conséquences néfastes au niveau individuel et de la population. En fait, les infections virales peuvent induire des dommages à différents organes de l’appareil génital masculin (AGM), compromettant ainsi la fertilité masculine. Le stress oxydatif, induit lors de l’inflammation locale et systémique à médiation virale, est responsable de lésions testiculaires, compromettant les fonctions des cellules germinales et endocrines. Une réduction de la concentration et de la motilité des spermatozoïdes, du nombre de spermatozoïdes normaux ainsi qu’une augmentation de la fragmentation de l’ADN, sont les résultats habituels retrouvés au cours des infections virales qui, cependant, régressent généralement après la clairance de l’infection. Dans certains cas, cependant, l’excrétion virale persiste pendant une longue période, ce qui entraîne une transmission sexuelle inattendue, même après la disparition de la charge virale sanguine.La récente épidémie de Zika et d’Ebola a montré à quel point l’AGM pouvait représenter un réservoir de virus émergents dangereux, et à quel point de nouvelles modalités de surveillance des survivants sont fortement nécessaires pour limiter la transmission virale au sein de la population générale. Dans la présente revue, nous avons examiné les preuves concernant la présence de virus pertinents, y compris émergents et réémergents, dans l’appareil génital masculin, leur voie d’entrée, leurs effets néfastes sur la fertilité masculine et le modèle d’excrétion virale dans le sperme.Nous avons également décrit des stratégies de laboratoire pour réduire le risque d’infection croisée horizontale ou verticale chez les couples sérodifférents qui ont recours à des techniques de procréation assistée.Mots-clés Voies génitales masculines, Virus, Fertilité masculine, Transmission sexuelle, Paramètres du Sperme.

Primary lymphoma of the male genital tract (PLMGT) is rare, and data on its epidemiology and prognosis are lacking. Our study aimed to estimate the incidence and develop a predictive nomogram for PLMGT. We pooled the incidence and survival data of PLMGT over the last 20 years from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates were calculated by year of diagnosis, age, race, and histology. Independent prognostic factors selected by Cox regression analysis were used to develop a nomogram for predicting overall survival (OS). Our study enrolled 1312 patients with PLMGT. The overall incidence rate of PLMGT was 0.437/1,000,000 during 2000-2019. OS was associated with age, marital status, histological subtype, Ann Arbor stage, and therapeutic strategy, which were used to construct nomograms to predict 1-, 3-, and 5-year OS rates. Receiver operating characteristic curves, calibration plots, and decision curve analysis showed good performance of the nomogram. Based on the total score of each patient from the nomogram, the patients were clustered into three risk groups, and the risk stratification model was more successful in predicting clinical outcomes than the traditional Ann Arbor staging system. The incidence rate of PLMGT has remained relatively stable over the past two decades. For the OS of patients with PLMGT, we established a novel predictive nomogram involving all independent risk factors obtained from the SEER database and developed a corresponding risk classification system that showed better predictive performance than the Ann Arbor staging system.

BACKGROUND: Infertility affects one couple out of six worldwide. Male infertilty can result from congenital or acquired factors, of which pathogens that reach the genital tract through sexual contact or blood dissemination. The impact of major viral, bacterial and parasitic infections on the male genital tract and fertility has been summarized.
CONCLUSIONS: A systematic review of articles published in the Google Scholar and PubMed databases was conducted. It turns out that viruses, as well as bacteria and parasites are major inducers of male genital tract infections and ensuing infertility through damage to the organs and subsequent loss of function and/or through direct damage to the sperm cells. Moreover, not only male infertility results from such infections but these can also be transmitted to women and even to the offspring, thus highlighting the need to efficiently detect, treat and prevent them.
RéSUMé: CONTEXTE: L’infertilité affecte un couple sur six dans le monde. L’infertilité masculine peut être due à des facteurs congénitaux ou acquis, parmi lesquels des pathogènes qui atteignent le tractus génital par contact sexuel ou dissémination par voie sanguine. Cette revue présente les principaux pathogènes d’origine virale, bactérienne et parasitaire qui affectent le tractus génital masculin et leur impact sur la fertilité. RéSULTATS ET CONCLUSION: Une revue systématique de la littérature a été conduite à partir de Google Scholar et de PubMed. Il apparaît que les virus, au même titre que les bactéries ou les parasites, sont des facteurs majeurs d’infection du tractus génital masculin et d’infertilité. Cette dernière découle de dommages aux organes reproducteurs et à leur perte de fonction et/ou d’atteintes directes aux spermatozoïdes. De plus, ces infections n’impactent pas seulement la fertilité masculine, mais elles peuvent également être transmises aux partenaires féminines et même à la descendance, ce qui souligne l’importance de les détecter, de les traiter et de les prévenir efficacement.

Sexually transmitted HIV infections in heterosexual men are acquired through the penis. Low adherence to condom usage and the fact that 40% of circumcised men are not protected indicate the need for additional prevention strategies. Here, we describe a new approach to evaluate the prevention of penile HIV transmission. We demonstrated that the entire male genital tract (MGT) of bone marrow/liver/thymus (BLT) humanized mice is repopulated with human T and myeloid cells. The majority of the human T cells in the MGT express CD4 and CCR5. Direct penile exposure to HIV leads to systemic infection including all tissues of the MGT. HIV replication throughout the MGT was reduced 100-1,000-fold by treatment with 4\'-ethynyl-2-fluoro-2\'-deoxyadenosine (EFdA), resulting in the restoration of CD4+ T cell levels. Importantly, systemic preexposure prophylaxis with EFdA effectively protects from penile HIV acquisition. IMPORTANCE Over 84.2 million people have been infected by the human immunodeficiency virus type 1 (HIV-1) during the past 40 years, most through sexual transmission. Men comprise approximately half of the HIV-infected population worldwide. Sexually transmitted HIV infections in exclusively heterosexual men are acquired through the penis. However, direct evaluation of HIV infection throughout the human male genital tract (MGT) is not possible. Here, we developed a new in vivo model that permits, for the first time, the detail analysis of HIV infection. Using BLT humanized mice, we showed that productive HIV infection occurs throughout the entire MGT and induces a dramatic reduction in human CD4 T cells compromising immune responses in this organ. Antiretroviral treatment with novel drug EFdA suppresses HIV replication in all tissues of the MGT, restores normal levels of CD4 T cells and is highly efficient at preventing penile transmission.

The human body is vastly colonised by microorganisms, whose impact on health is increasingly recognised. The human genital tract hosts a diverse microbiota, and an increasing number of studies on the male genital tract microbiota suggest that bacteria have a role in male infertility and pathological conditions, such as prostate cancer. Nevertheless, this research field remains understudied. The study of bacterial colonisation of the male genital tract is highly impacted by the invasive nature of sampling and the low abundance of the microbiota. Therefore, most studies relied on the analysis of semen microbiota to describe the colonisation of the male genital tract (MGT), which was thought to be sterile. The aim of this narrative review is to present the results of studies that used next-generation sequencing (NGS) to profile the bacterial colonisation patterns of different male genital tract anatomical compartments and critically highlight their findings and their weaknesses. Moreover, we identified potential research axes that may be crucial for our understanding of the male genital tract microbiota and its impact on male infertility and pathophysiology.

The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (Cmax, tmax) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues.

The male genital tract is diverse among vertebrates, but its development remains unclear, especially in the rete region. In this study, we investigated the testis-mesonephros complex of rabbit, chicken, and frog (Xenopus tropicalis) by immunohistochemistry for markers such as Ad4BP/Sf-1 (gonadal somatic and rete cells in mammals) and Pax2 (mesonephric tubules), and performed a three-dimensional reconstruction. In all investigated animals, testis cords were bundled at the mesonephros side. Rete cells positive for Ad4BP/Sf-1 (rabbit) or Pax2 (chicken and frog) were clustered at the border region between the testis and mesonephros. The cluster possessed two types of cords; one connected to the testis cords and the other to the mesonephric tubules. The latter rete cords were contiguous to Bowman\'s capsules in rabbit and chicken but to nephrostomes in frog. In conclusion, this study showed that mammals, avian species, and frogs commonly develop the bundle between the testis cords (testis canal) and the cluster of rete cells (lateral kidney canal), indicating that these animals share basic morphogenesis in the male genital tract. The connection site between the rete cells and mesonephric tubules is suggested to have changed from the nephrostome to the Bowman\'s capsule during vertebrate evolution from anamniote to amniote.

OBJECTIVE: We want to evaluate the possible presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in semen samples and semen quality, looking for a possible relationship between the infectious disease and fertility.
METHODS: In this prospective study, we enrolled 15 consecutive men (age 18-50 years) with positive oropharyngeal swab to SARS-CoV-2 and classified, according to WHO criteria, in mild to moderate disease. A semen sample was collected to detect SARS-CoV viral RNA by the automated Real-Time PCR ELITe InGenius® system and the GeneFinderTM COVID-19 Plus RealAmp Kit assay (ELITechGroup, France). Analysis of semen characteristics was performed according to WHO laboratory manual 5th ed. for the examination and processing of human semen. Blood samples for the dosage of hormonal assay, procalcitonin, interleukin 6, C-reactive protein were obtained.
RESULTS: SARS-CoV-2 RNA has not been detected in semen samples from any of the subjects analysed. Sperm analysis exhibited abnormal seminal values in 14 out of 15 patients (93.3%). Furthermore, no difference was detected regarding sperm quality between mild and moderate SARS-CoV-2 patients. No alteration in the inflammatory indices was observed in the studied population, as well gonadotropins and testosterone levels.
CONCLUSIONS: COVID patients studied exhibits alteration of the seminal fluid both in microscopic and macroscopic characteristics such as hypoposia and increased viscosity, which have not been detected in previous studies. The presence of viral RNA within the seminal fluid was excluded.