Testicular Infection Research Articles

Comparison of Perioperative Analgesic Efficacy of Lidocaine Intratesticular Block and Spermatic Cord Instillation in Feline Castration

Intratesticular block is an effective local anesthetic technique for castration; however, its use may be limited in cases of testicular masses or infections. Instillation is a simple technique used in several procedures, though studies investigating its application in feline castration remain scarce. Therefore, this study aimed to compare the perioperative analgesic efficacy of lidocaine intratesticular block and spermatic cord instillation in feline castration. Forty-five male cats were randomly divided into three groups: the intratesticular block group (IT), the spermatic cord instillation group (S), and the control group (C). All cats were anesthetized using the same protocol and both techniques were performed based on group assignments. Lidocaine (2 mg/kg) was administrated according to the designated route, while 0.9% normal saline was used for the alternative route and in the C group. Intraoperative parameters were recorded, showing that noninvasive blood pressure in the IT and S groups was significantly lower than in the C group. Although both lidocaine intratesticular block and spermatic cord instillation effectively reduce surgical noxious stimulation, intratesticular block is recommended as it provides more stable intraoperative vital signs and less postoperative pain. Therefore, spermatic cord instillation can be considered as an optional technique for managing pain in feline castration.

Possible mechanisms of spermatogenic dysfunction induced by viral infections: Insights from COVID-19.

As the COVID-19 pandemic nears resolution in 2024, the mechanisms by which SARS-CoV-2 and other viral infections induce spermatogenic dysfunction remain poorly understood. This review examines the mechanisms by which viral infections, particularly COVID-19, disrupt spermatogenesis and highlights the implications for male reproductive health. While reports suggest that spermatogenic dysfunction caused by COVID-19 is mild and transient, these findings may have broader applications in understanding and treating spermatogenic dysfunction caused by future viral infections. The PubMed database was searched to identify original and review articles investigating the mechanisms by which viral infections, particularly SARS-CoV-2, contribute to spermatogenic dysfunction. SARS-CoV-2 affects the testis through multiple mechanisms, including ACE2 receptor-mediated entry, direct viral damage, inflammatory response, blood-testis barrier disruption, hormonal imbalance, oxidative stress, and impaired spermatogenesis. The combination of these factors can disrupt testicular function and highlights the complexity of the effects of COVID-19 on male reproductive health. COVID-19 may disrupt spermatogenesis through direct testicular infection, systemic inflammation, hormonal disruption, and oxidative stress. Ongoing research, vaccination efforts, and clinical vigilance are essential to address these challenges and develop effective treatment and prevention strategies.

Point-of-Care Ultrasound Diagnosis of Pyocele: A Rare Complication of Testicular Infection

BackgroundEpididymo-orchitis is one of the common causes of acute scrotal pain that requires an accurate diagnosis as delayed management can result in complications such as pyocele, abscess, or testicular infarction. Point-of-care ultrasound (PoCUS) has emerged as a valuable diagnostic tool in the management of testicular emergencies in the emergency department (ED) including testicular infections Case ReportHere we report a case of an elderly man who presented to the ED with a complaint of right-sided testicular pain and swelling. The diagnosis of pyocele was made using a PoCUS, facilitating an early referral to urology services.Why should an emergency physician be aware of this case?In conclusion, this case underscores the important role of PoCUS in the timely and accurate diagnosis of pyocele. The prompt identification of pyocele enabled early referral to urology services, highlighting the significance of integrating PoCUS into the management of testicular emergencies in the ED.

Traumatic scrotal sac hematoma after a fall injury

Introduction and Importance: Traumatic scrotal sac hematoma is an uncommon medical condition following a fall injury. Symptoms include swelling, pain, and discoloration. Accurate and immediate diagnosis is crucial to avoid complications and prevent testis loss, abscess formation, erectile dysfunction, and infection. This case highlights the importance of prompt evaluation and treatment to prevent complications and ensure optimal patient outcomes. Case Presentation: A 56-year-old man without prior medical history presented to the emergency department with scrotal pain and swelling 10 h after a traumatic event. The patient underwent a series of examinations, including radiological studies, before undergoing scrotal exploration and hematoma evacuation under subarachnoid block anesthesia. As of now, the patient has not experienced any complications that have impacted his quality of life. Clinical Discussion: Scrotal sac hematoma is formed following a blunt trauma when a significant force is transferred during contact with a solid object, impact from sports equipment, road traffic accidents, or falls from a height. If early exploration is delayed, then it can lead to complications like testicular atrophy, abscess formation, and infection. Hence, prompt diagnosis with clinical and radiological evaluation followed by immediate surgical intervention can result in better outcomes. Conclusion: Scrotal sac hematoma from blunt trauma is rare but can cause significant morbidity and psychological distress. Early surgical intervention is often necessary, especially if a testicle has ruptured, to salvage viable testicular tissue and control bleeding, resolve pain faster, shorten hospital stays, and improve the quality of life for patients.

Study of the protective effect of ginseng against testicular oxidative stress biomarkers and its gene expression induced by ciprofloxacin

Ciprofloxacin is the first-choice member of the fluoroquinolone antibacterials for treating testicular infections, but it may harm testicular tissue because of oxidative stress. Many mechanisms are involved, like decreasing antioxidant enzymes and suppressing gene expression. This study intends to investigate the possible protective role of ginseng against ciprofloxacin-induced testicular oxidative stress and its mechanism, if any. For this purpose, 50 adult male albino rats were randomly divided into five groups, ten rats in each group. Rats in group 1 received only ciprofloxacin at a daily dose of 156.46 mg/kg. Rats in groups 2, 3 and 4 received ciprofloxacin in a daily dose of 156.46 mg/kg, ginseng in two doses of 100 and 200 mg/kg, and vitamin E as a standard in a daily dose of 100 mg/kg, respectively. Group 5 served as control and received carboxymethylcellulose in normal saline. All these treatments were applied orally during 14 14-day experimental courses. Half the animals in each group were euthanized on day 15 from the start of the treatment, while the second half was euthanized on day 60. Both testes were dissected, immediately frozen, and evaluated for oxidative stress biomarkers and gene expression antioxidant enzymes. We found that ciprofloxacin significantly (P ≤ 0.05) increased MDA and decreased total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) compared to the control group. Also, the drug downregulated gene expression of SOD and CAT. Compared to all groups, the co-administration of ginseng or vitamin E with ciprofloxacin almost normalized antioxidant enzymes and upregulated the tested gene expressions. It could be concluded that ginseng ameliorates the testicular adverse effect of ciprofloxacin. So, it is highly recommended to be used as an adjunct remedy during ciprofloxacin administration for its antioxidant properties. Keywords: Ciprofloxacin, Gene expression, Ginseng, Infertility, ROS, Testicular oxidative stress, Vitamin-E.

SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo.

SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.

Coronavirus Disease Patients with Acute Testicular Infection: Ultrasound Imaging Findings

Introduction: Objectives: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, raising widespread public health concerns. Our team treated hospitalized patients with COVID-19 in SAIMS Indore, where the outbreak first began, and we suspected that SARS-CoV-2 may cause testicular infection in male patients. We conducted this study to explore that observation. Methods: We enrolled male patients with a confirmed diagnosis of COVID-19 and performed a bedside ultrasound (US) examination of the scrotum, focused on findings of acute inflammation such as tunica albuginea thickening, enlargement and heterogeneous echogenicity of the testis, epididymis, or both, an abscess, scrotal wall edema, and hydrocele. Then we compared the proportions of observed epididymo-orchitis in patients from different age groups and COVID-19 severity groups. Results: A total of 150 patients with COVID-19 were enrolled in our study, and 32 (22.5%) patients had acute orchitis, epididymitis, or epididymo-orchitis on scrotal US imaging, according to the diagnosis criteria. The observed risk of acute scrotal infection increased with age, with the incidence reaching 53.3% in men older than 80 years. We also observed that men with severe COVID-19 had a significantly higher possibility of epididymo-orchitis compared to the non- severe COVID-19 group (P = .037). Conclusions: This study shows US imaging evidence that SARS-CoV-2 may cause infection of the testis or epididymis, and the risk is worthy of the attention of clinicians.

Lycopene alleviates lipopolysaccharide-induced testicular injury in rats by activating the PPAR signaling pathway to integrate lipid metabolism and the inflammatory response.

Male fertility can be hampered by systemic and testicular infections and inflammation, which can lead to impaired spermatogenesis that often cannot be reversed by antibiotic treatment. There has been some suggestion that lycopene (LYC) may be useful in the preservation of fertility, although its mechanisms are complex. This current study examined the therapeutic efficacy of LYC on testicular damage and its underlying mechanisms. Lipopolysaccharide (LPS; 5 mg/kg) was injected intraperitoneally to induce inflammation of the testes in mature male rats. The rats in the experimental group were administered 5 mg/kg LYC intragastrically for 4 weeks. The testes were harvested from the euthanized rats for lipidomics, RNA sequencing, and related experimental tests. Laboratory data suggested that LPS-induced systemic inflammation induced cytokine excess and oxidative stress in the testes. Administration of oral LYC inhibited the excess cytokine production and oxidative stress, mitigating damage to the testes. Lipidomic studies identified significant changes to 258 lipids and 5 metabolism pathways. Coupled with RNA sequencing analysis, 1,116 genes were found to be significantly regulated and many lipid metabolism-related signaling pathways were identified. The expression of retinoid X receptor alpha (RXR) in the peroxisome proliferator-activated receptor (PPAR) signaling pathway was significantly upregulated after LYC treatment, which activated the RXR/PPAR easy dimer. The expression of downstream genes such as fatty acid binding protein 3 (FABP3) and carnitine palmitoyltransferase 1A (CPT1A) was increased. These genes are involved in the control of fatty acid metabolism, fatty acid degradation, fatty acid chain elongation, and lipid metabolism, which partially explains the changes in the content and composition of lipids. LYC regulates the lipid metabolism of testes and lipid metabolism-related signaling pathways, such as the PPAR signaling pathway. Furthermore, LYC ameliorated the LPS-induced dysregulation of lipid metabolism in the testes, as well as the LPS-induced inflammatory response. This study offers a new perspective for the investigation of the mechanisms in inflammatory testicular damage and potential therapeutic targets.

Dirofilaria repens Testicular Infection in Child, Italy.

Testicular Dirofilaria repens infection was identified and confirmed by sequence analysis in a child in northeastern Italy. Because human dirofilariasis is emerging in southern and eastern Europe, this parasitic infection should be considered in the differential diagnosis of scrotal swelling in disease-endemic countries to avoid unnecessary interventions, such as orchiectomy.

A Hidden Testicular Mass at Ultrasound

A 20-year-old young man was referred to our department for a self-detected palpable, painless testicular mass. The patient reported a steroid-resistant nephrotic syndrome and ulcerative colitis since 2003 treated with Azathioprine and Infliximab and denied any history of testicular infection or trauma. Exam showed a well circumscribed, non-tender, soft mass on the right testicle. Scrotal ultrasonography (US) showed a homogeneous testis with normal echogenicity and of normal volume with the exception of a focal buldging (Fig.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage.

BackgroundThe role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain.MethodsWe investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control.ResultsBesides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, and serum testosterone and inhibin B at 4 to 7 days post-infection (dpi), and subsequently reduced testicular size and weight, and serum sex hormone level at 42 to 120 dpi. Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. These testicular damages can be prevented by vaccination.ConclusionsSARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.

Adjustable Transobturator Male System (ATOMS) Infection: Causative Organisms and Clinical Profile

ObjectiveTo evaluate the clinical profile and the organisms producing adjustable transobturator male system (ATOMS) infection in a contemporary series. MethodsMulticenter retrospective study evaluating patients undergoing ATOMS explant for clinical signs of infection from a series of 902 patients treated in 9 academic institutions. Clinical and microbiological data were evaluated. ResultsInfection presented in 24 patients (2.7%). The median age was 73 ± 7yrs and the median interval from ATOMS implantation to explant 11 ± 26.5mo. Infection was diagnosed within 3-months after surgery in 7(29.2%). Scrotal port erosion was present in 6 cases (25%) and systemic symptoms of parenchymatous testicular infection in 2(8.3%). The culture of the periprosthetic fluid was positive in 20(83.3%): 12(50%) Gram-negative bacteria, 9(37.5%) Gram-positive cocci and 1(4.2%) yeast. The most frequent isolates were Enterococcus and Proteus sp. (16.7% each), followed by Pseudomona sp. and S. epidermidis (12.5% each). Methicillin resistant S. aureus was detected only in 1 case (4.2%). Despite the infection 17 patients (70.8%) were satisfied with the implant and 18(75%) received a second device (11 repeated ATOMS and 7 AUS) at a median 9.7 ± 12.6mo after explant. Limitations include retrospective design and lack of microbiological cultures in ATOMS explanted for non-infective cause. ConclusionInfection of a prosthetic device is a disturbing complication. A proportion of patients with ATOMS infection is associated to scrotal port erosion and/or parenchymatous urinary tract infection. Enterococcus and Proteus sp. are the most common organisms producing ATOMS infection and this could have implications for the selection of the most appropriate surgical prophylaxis.

Uropathogenic Escherichia coli Infection Compromises the Blood-Testis Barrier by Disturbing mTORC1-mTORC2 Balance.

The structural and functional destruction of the blood-testis barrier (BTB) following uropathogenic E. coli (UPEC) infection may be a critical component of the pathologic progress of orchitis. Recent findings indicate that the mammalian target of the rapamycin (mTOR)-signaling pathway is implicated in the regulation of BTB assembly and restructuring. To explore the mechanisms underlying BTB damage induced by UPEC infection, we analyzed BTB integrity and the involvement of the mTOR-signaling pathway using in vivo and in vitro UPEC-infection models. We initially confirmed that soluble virulent factors secreted from UPEC trigger a stress response in Sertoli cells and disturb adjacent cell junctions via down-regulation of junctional proteins, including occludin, zonula occludens-1 (ZO-1), F-actin, connexin-43 (CX-43), β-catenin, and N-cadherin. The BTB was ultimately disrupted in UPEC-infected rat testes, and blood samples from UPEC-induced orchitis in these animals were positive for anti-sperm antibodies. Furthermore, we herein also demonstrated that mTOR complex 1 (mTORC1) over-activation and mTORC2 suppression contributed to the disturbance in the balance between BTB “opening” and “closing.” More importantly, rapamycin (a specific mTORC1 inhibitor) significantly restored the expression of cell-junction proteins and exerted a protective effect on the BTB during UPEC infection. We further confirmed that short-term treatment with rapamycin did not aggravate spermatogenic degeneration in infected rats. Collectively, this study showed an association between abnormal activation of the mTOR-signaling pathway and BTB impairment during UPEC-induced orchitis, which may provide new insights into a potential treatment strategy for testicular infection.

Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities.

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes.

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.

Potential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIV.

Viruses have colonized the germ line of our ancestors on several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few nonretroviruses. Among the recently emerged viruses infecting humans, several target the testis (e.g., human immunodeficiency virus [HIV], Zika virus, and Ebola virus). Here, we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in vitro Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration, and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and simian immunodeficiency virus (SIV) DNA were detected within a few TGCs in the testis from one infected patient, one rhesus macaque, and one African green monkey in vivo Molecular landscape analysis revealed that early TGCs were enriched in HIV early cofactors up to integration and had overall low antiviral defenses compared with testicular macrophages and Sertoli cells. In conclusion, our study reveals that TGCs can support the entry and integration of HIV upon cell-associated infection. This could represent a way for this contemporary virus to integrate into our germ line and become endogenous in the future, as happened during human evolution for a number of viruses.IMPORTANCE Viruses have colonized the host germ line on many occasions during evolution to eventually become endogenous. Here, we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro Our results indicate that isolated primary TGCs express alternative HIV-1 receptors, allowing virion binding but not entry. However, HIV-1 entered and integrated into TGCs upon cell-associated infection and produced low levels of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication, including integration, suggesting potential for endogenization in future generations.

Ultrasound Imaging Findings of Acute Testicular Infection in Patients With Coronavirus Disease 2019: A Single-Center-Based Study in Wuhan, China.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, raising widespread public health concerns. Our team treated hospitalized patients with COVID-19 in Wuhan, where the outbreak first began, and we suspected that SARS-CoV-2 may cause testicular infection in male patients. We conducted this study to explore that observation. We enrolled male patients with a confirmed diagnosis of COVID-19 and performed a bedside ultrasound (US) examination of the scrotum, focused on findings of acute inflammation such as tunica albuginea thickening, enlargement and heterogeneous echogenicity of the testis, epididymis, or both, an abscess, scrotal wall edema, and hydrocele. Then we compared the proportions of observed epididymo-orchitis in patients from different age groups and COVID-19 severity groups. A total of 142 patients with COVID-19 were enrolled in our study, and 32 (22.5%) patients had acute orchitis, epididymitis, or epididymo-orchitis on scrotal US imaging, according to the diagnosis criteria. The observed risk of acute scrotal infection increased with age, with the incidence reaching 53.3% in men older than 80 years. We also observed that men with severe COVID-19 had a significantly higher possibility of epididymo-orchitis compared to the nonsevere COVID-19 group (P = .037). This study shows US imaging evidence that SARS-CoV-2 may cause infection of the testis or epididymis, and the risk is worthy of the attention of clinicians.

Zika virus tropism during early infectionof thetesticular interstitium and its role in viral pathogenesis in the testes.

Sexual transmission and persistence of Zika virus (ZIKV) in the testes pose new challenges for controlling virus outbreaks and developing live-attenuated vaccines. It has been shown that testicular infection of ZIKV is initiated in the testicular interstitium, followed by spread of the virus in the seminiferous tubules. This leads to testicular damage and/or viral dissemination into the epididymis and eventually into semen. However, it remains unknown which cell types are targeted by ZIKV in the testicular interstitium, and what is the specific order of infectious events leading to ZIKV invasion of the seminiferous tubules. Here, we demonstrate that interstitial leukocytes expressing mir-511-3p microRNA are the initial targets of ZIKV in the testes, and infection of mir-511-3p-expressing cells in the testicular interstitium is necessary for downstream infection of the seminiferous tubules. Mir-511-3p is expressed concurrently with CD206, a marker of lineage 2 (M2) macrophages and monocyte derived dendritic cells (moDCs). Selective restriction of ZIKV infection of CD206-expressing M2 macrophages/moDCs results in the attenuation of macrophage–associated inflammatory responses in vivo and prevents the disruption of the Sertoli cell barrier in vitro. Finally, we show that targeting of viral genome for mir-511-3p significantly attenuates early ZIKV replication not only in the testes, but also in many peripheral organs, including spleen, epididymis, and pancreas. This incriminates M2 macrophages/moDCs as important targets for visceral ZIKV replication following hematogenous dissemination of the virus from the site of infection.

Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development†.

With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality.

Hematogenous dissemination of Chlamydia muridarum from the urethra in macrophages causes testicular infection and sperm DNA damage†

The incidence of Chlamydia infection, in both females and males, is increasing worldwide. Male infections have been associated clinically with urethritis, epididymitis, and orchitis, believed to be caused by ascending infection, although the impact of infection on male fertility remains controversial. Using a mouse model of male chlamydial infection, we show that all the major testicular cell populations, germ cells, Sertoli cells, Leydig cells, and testicular macrophages can be productively infected. Furthermore, sperm isolated from vas deferens of infected mice also had increased levels of DNA damage as early as 4 weeks post-infection. Bilateral vasectomy, prior to infection, did not affect the chlamydial load recovered from testes at 2, 4, and 8 weeks post-infection, and Chlamydia-infected macrophages were detectable in blood and the testes as soon as 3 days post-infection. Partial depletion of macrophages with clodronate liposomes significantly reduced the testicular chlamydial burden, consistent with a hematogenous route of infection, with Chlamydia transported to the testes in infected macrophages. These data suggest that macrophages serve as Trojan horses, transporting Chlamydia from the penile urethra to the testes within 3 days of infection, bypassing the entire male reproductive tract. In the testes, infected macrophages likely transfer infection to Leydig, Sertoli, and germ cells, causing sperm DNA damage and impaired spermatogenesis.