Search Results (148)

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

The aim of this study was to analyze the influence of season (rut and non-rut) on the antioxidant status of selected reproductive tissues in male European red deer (Cervus elaphus elaphus). Tissue samples were collected post mortem from the testes and epididymides (caput, corpus, and cauda) of 24 animals. The activity of antioxidant enzymes (superoxide dismutase—SOD, glutathione peroxidase—GPx, and catalase—CAT) and the mRNA expression of SOD1, SOD2, SOD3, GPx4, GPx5, and CAT were examined. In addition, these proteins were identified by western blot. ANOVA revealed that season, type of tissue, and the interaction between these factors significantly (p ≤ 0.05) influenced the activity and mRNA expression of the analyzed enzymes. The activity of SOD and GPx peaked in the corpus epididymis in the rut season and in the caput epididymis in the non-rut season. Regardless of season, the relative abundances of GPx4, SOD1, SOD2, and SOD3 mRNA were highest in the testis, and GPx5 mRNA—in the caput epididymis. The activity of SOD and CAT was significantly higher during the non-rut season compared with the rut season, but only in the caput epididymis. This study demonstrated that the activity of antioxidant enzymes and the relative mRNA expression varies across tissues and seasons to provide the reproductive system of European red deer with the required antioxidant protection. Further research is needed to expand our understanding of the antioxidant defense system in the reproductive tract of European red deer. Full article

Goji berries (Lycium barbarum), rich in antioxidant and immunomodulatory compounds, have shown potential benefits for male reproductive health. This study aimed to evaluate the impact of dietary Goji berry (GB) supplementation on immune-related and antioxidant gene expression in the male reproductive tract of rabbits. Eighteen 7-month-old New Zealand White rabbit bucks were randomly assigned to two groups: a control group (n = 9) receiving a standard diet, and a Goji group (n = 9) receiving the same diet supplemented with 1% GB. After 60 days of nutritional adaptation and then 60 days of treatment, tissues from the testes, epididymis, seminal vesicles, prostate, and bulbourethral glands were collected and analyzed using quantitative real-time PCR. Gene expression analysis focused on immune markers (TLR4, IL-1β, IL-10, and TNFα) and antioxidant enzymes (SOD1, CAT, and GPX). Significant modulation was observed only in the epididymis, where TLR4 and GPX were significantly downregulated in the Goji group (p = 0.0274 and p = 0.007, respectively), while IL-1β and TNFα showed a downward trend. No significant differences were found in the other tissues. These results suggest that Goji berry supplementation exerts tissue-specific effects, particularly in the epididymis, by modulating inflammation and oxidative stress. This supports its potential use as a natural nutraceutical strategy to enhance male fertility in rabbits. Full article

Unilateral renal agenesis (URA) is a urinary tract congenital anomaly characterized by a congenital absence or early developmental arrest of only one kidney. In the presence of a normal contralateral kidney, URA is typically considered a condition of minimal clinical significance as the solitary kidney often undergoes hypertrophy and can sufficiently perform the needed renal function after birth. However, postnatal studies suggest that URA has a significant association with other urinary and extra-urinary anomalies and may have implications for long-term health. This descriptive review focuses on the perinatal aspects of URA, emphasizing the main ultrasound findings to establish the prenatal diagnosis and to guide perinatal management. The pediatric implications of this diagnosis, particularly the high prevalence of long-term complications including hypertension, proteinuria, and a decreased glomerular filtration rate, are also briefly reviewed. URA is consistently associated with other ipsilateral urogenital anomalies. In females, there is a significant association with uterine anomalies that has significant implications for subsequent reproductive function. In males, the prevalence of both urinary and genital anomalies is also increased, which may also have implications for future fertility. Prenatal ultrasound offers the possibility of early diagnosis and parental counseling, which may result in timely intervention to reduce contralateral renal damage, prevent severe urogenital manifestations and co-morbidities, and improve fertility and the quality of life. Full article

Seminal plasma, traditionally regarded as a passive transport medium for sperm, has emerged as a sophisticated biofluid orchestrating critical dialogues in reproductive physiology. Contemporary research reveals its multifunctional role in modulating endometrial receptivity through molecular priming of the female reproductive tract, a process essential for successful embryo implantation. Notably, seminal plasma contains numerous extracellular vesicles (EVs) that serve as critical mediators of intercellular communication via the regulation of biological processes in target cells. Through this sophisticated vesicular communication system, seminal plasma extracellular vesicles (SPEVs) coordinate critical reproductive events. Thus, it will be important to elucidate the molecular mechanisms by which SPEVs mediate reproductive processes, to provide knowledge that may improve fertility outcomes. Herein, we elucidated the emerging potential of SPEVs as non-invasive biomarkers for male fertility assessment and infertility diagnosis. Furthermore, this review systematically summarized current advances in SPEVs, highlighting their multifaceted roles in mediating sperm maturation, regulating sperm capacitation, and modulating embryo implantation through targeted delivery of bioactive signaling molecules. Full article

Extracellular Vesicles (EVs) from seminal plasma have achieved attention due to their potential physiopathological role in male reproductive systems. This study employed a comprehensive proteomic and transcriptomic approach to investigate the composition and molecular signatures of EVs isolated from human seminal plasma. EVs from Normozoospermic (NORMO), OligoAsthenoTeratozoospermic (OAT), and Azoospermic (AZO) subjects were isolated using a modified polymer precipitation-based protocol and characterized for size and morphology. Comprehensive proteomic analysis, using both gel-free and gel-based approaches, revealed distinct protein profiles in each group (p<0.01), highlighting potential molecules and pathways involved in sperm function and fertility. The data are available via ProteomeXchange with identifiers PXD051361 and PXD051390, respectively. Transcriptomic analysis confirmed the trend of a general downregulation of AZO and OAT compared to NORMO shedding light on regulatory mechanisms of sperm development. Bioinformatic tools were applied for functional omics analysis; the integration of proteomic and transcriptomic data provided a comprehensive understanding of the cargo content and regulatory networks present in EVs. This study contributes to elucidating the key role of EVs in the paracrine communication regulating spermatogenesis. A full understanding of these pathways not only suggests potential mechanisms regulating male fertility but also offers new insights into the development of diagnostic tools targeting male reproductive disorders. Full article

Trichomonas vaginalis, the protozoan responsible for trichomoniasis, encounters fluctuating levels of metal cations in the male urogenital tract, notably zinc (Zn²⁺) and cadmium (Cd²⁺), which may induce genotoxic stress. While zinc is a key physiological component of the male reproductive tract, both Zn²⁺ and Cd²⁺ can become genotoxic at elevated concentrations. However, their effect on DNA repair mechanisms in T. vaginalis remains poorly understood. This study characterizes, for the first time, the expression and modulation of the recombinase TvRAD51, a homologous recombination (HR) key enzyme, in response to UV irradiation and sublethal concentrations of Zn²⁺ (1.6 mM) and Cd²⁺ (0.1 mM). In silico analyses confirmed the presence and conserved structure of the tvrad51 gene and its interaction with HR-related proteins, such as TvBLM and TvBRCA2. Quantitative RT-PCR, Western blot, and immunofluorescence assays revealed that TvRAD51 is upregulated at both transcript and protein levels following UV- and cation-induced DNA damage, with distinct temporal expression patterns for Zn²⁺ and Cd²⁺ exposure. Notably, TvRAD51 showed nuclear localization at early time points post-exposure, suggesting active participation in DNA repair processes. These findings demonstrate that TvRAD51 is a central component of the genotoxic stress response in T. vaginalis, potentially contributing to parasite survival and adaptation in hostile environments through homologous recombination repair pathways. Full article

Sperm preparation is a critical step in assisted reproduction, aiming to isolate spermatozoa with optimal characteristics and high fertilizing potential. Traditional sperm selection methods involve centrifugation, which may cause sperm damage. Microfluidic sperm sorting (MSS) offers an alternative approach, mimicking the female reproductive tract environment, avoiding centrifugation, and reducing manipulation and processing time. This study aims to compare the performance of MSS and Swim-up (SU) in 26 normozoospermic, 31 hyperviscous normozoospermic, 15 oligozoospermic, and 9 asthenozoospermic subjects. Semen samples were collected from male subjects undergoing routine semen analysis at Careggi University Hospital, Florence. Sperm selection was carried out using both SU and MSS. The parameters assessed included sperm motility, viability, concentration, kinematics, DNA fragmentation (sDF), chromatin compaction, and oxidative status. Both SU and MSS improved sperm characteristics compared to unselected samples. MSS isolated high-quality spermatozoa with lower sDF and higher chromatin compaction than SU, not only in normozoospermic samples but also in samples with semen defects like hyperviscosity, low concentration and/or motility, and high sDF. In conclusion, the use of microfluidics may enhance the chances of successful fertilization and improve reproductive outcomes, especially for individuals with compromised semen quality where conventional methods may fail. Full article

Diethylstilbestrol (DES) is a synthetic non-steroidal estrogen, which was widely used to prevent preterm birth and abortion from the 1940s to the 1970s. DES can increase the incidence of infertility, the abnormal reproductive tract, and autoimmune diseases. However, the mechanism underlying DES on early pregnancy in mice is unclear. This study evaluated the effects of DES on early pregnancy in mice, especially on uterine receptivity and decidualization. Newborn female mice were subcutaneously injected with 0.1 mg/kg DES, 1 mg/kg DES, or sesame oil as controls for 5 consecutive days. At 6 weeks old, these female mice were mated with 8–12-week-old fertile males to obtain pregnancy. The uteri of these mice were collected on days 4, 5, and 8 of pregnancy for further analysis. On days 5 and 8 of pregnancy, the number of implantation sites in 0.1 mg/kg DES group is similar to the control group, while almost no implantation sites are detected in the 1 mg/kg DES group. On day 4 of pregnancy, there was no significant difference in uterine receptive molecules between the control group and the 0.1 mg/kg DES group. However, the levels of uterine receptive molecules in the 1 mg/kg DES group are abnormal. In addition, 6 μM DES significantly inhibits mouse in vitro decidualization. The excessive activation of pyroptosis may lead to pregnancy failure. The pyroptosis-related molecules in the 1 mg/kg DES group were significantly up-regulated, suggesting that DES may contribute to pregnancy failure by over-activating pyroptosis. Full article

A 10-month-old pygmy goat was examined at the Royal (Dick) School of Veterinary Studies at the University of Edinburgh in January 2022, having been referred with a suspected diagnosis of a disorder of sexual development (DSD). The animal displayed a predominantly female phenotype (vulva with enlarged clitoris and vagina) but some male external characteristics such as a beard, larger body size, and larger horns. It also typically exhibits male behaviours such as mounting, aggression, and flehmen response. Computed tomography (CT) detected a bicornuated tubular fluid-filled structure connected to bulbous soft tissue masses. Subsequent exploratory laparotomy and reproductive tract removal identified underdeveloped uterine horns connected to ductus deferens and gonads, which were confirmed as testicles by histological examination. No spermatogenesis was detected, and no ovarian tissue was apparent. Blood levels of testosterone showed a marked decrease post-surgery (2.10 nmol/L to <0.03 nmol/L). Whole genome sequencing suggested that the patient may have an XY male karyotype, although cytological analysis was not possible to confirm the XY karyotype. Full article

The Rhox family of homeobox transcription factors comprises established regulators of gonad function, but their downstream targets have been relatively elusive, particularly in the female reproductive tract. Here, we characterize Ins2 as a downstream target of the two granulosa cell-specific factors, Rhox5 and Rhox8, in the ovary. While INS2 is classically produced by islet cells in the pancreas, we found that Ins2 gene expression is present in the mural granulosa cell layer of large antral follicles, and it was not significantly reduced in Rhox5-null mice. This was a surprising finding as we previously validated Ins2 as a direct target of RHOX5 in Sertoli cells, the male counterpart to granulosa cells that serves the germ cell nurse function in the testis. In the ovary, RHOX8 appears to be the major driver of Ins2 expression, as evidenced from the maximal activity of Ins2 promoter reporter plasmids when RHOX8 protein was active within granulosa cells in vitro and the downregulation of endogenous Ins2 in mice with the granulosa cell-specific knockdown of RHOX8 in vivo. RHOX5 induces Rhox8 expression in pre-antral granulosa cells and then becomes relatively silent in peri-ovulatory follicles. However, Rhox8 does not peak until after the ovulatory LH surge. The induction of Rhox8 by progesterone, after the normal window of RHOX5 has passed, may explain why Rhox5-null female mice display apparently normal fertility, if RHOX8 is capable of the redundant stimulation of target genes that are essential for ovulation. Full article

Viral infections of the reproductive tract and testis in male yaks, often resulting from natural mating under grazing conditions, can lead to infertility due to Leydig cell (LC) apoptosis, immune activation, oxidative stress, and reduced testosterone production. Spermidine (SPD), a potential therapeutic agent with antioxidant and anti-aging properties, might alleviate oxidant stress, immune response, and virus infection caused by apoptosis. In this study, firstly testicular Leydig cells of yak were induced with Poly(I:C), the pathogen-associated molecular pattern of the dsRNA virus, as a pathogenic model at the cellular level. Secondly, immune response, apoptosis, oxidative stress, and testosterone synthesis were measured in LC with or without SPD culture medium. Finally, transcriptomic sequencing was utilized to investigate the molecular mechanisms underlying the protective effects of SPD. These results suggested Poly(I:C) damaged the function of Leydig cells, significantly decreased the concentration of testosterone, and induced immune response, oxidative stress, and cell apoptosis, while SPD significantly alleviated the immune response and oxidative stress, and then significantly inhibited cell apoptosis and restores testosterone production in LCs. Transcriptomic analysis revealed that SPD significantly alleviates inflammation and apoptosis induced by Poly(I:C), reducing immune response and cellular damage through the regulation of several key gene expressions. These findings suggest SPD has the potential ability to mitigate Poly(I:C)-induced immune response, oxidative stress, and apoptosis, and then restore testosterone production in Leydig cells, offering a promising strategy to protect and enhance male yak fertility after infection with dsRNA virus. Full article

Background/Objectives: Male infertility is a complex, multifactorial condition influenced by infectious, inflammatory, and autoimmune components. Immunological factors, though implicated in reproduction, remain poorly understood. This study aims to deepen the understanding of infections, inflammation, and autoimmune factors in male infertility, with a focus on immune-related disorders affecting the testes and epididymis—immunologically privileged but vulnerable sites. These factors can impair sperm quality through oxidative stress (ROS) and antisperm antibodies (ASA), further compromising fertility. Methods: A narrative review was conducted by analyzing scientific literature from the past 10 years conducted on PubMed using keywords such as “male infertility”, “autoimmunity”, and “inflammatory disease”. Studies focusing on testicular and epididymal disorders, immunological impacts, and therapeutic approaches were included. Results: Our research highlights that conditions like epididymitis, vasectomy, testicular trauma, and previous surgeries can trigger inflammatory responses, leading to ASA formation and oxidative stress. ASA, particularly sperm-immobilizing antibodies, inhibits sperm motility and migration in the female reproductive tract. Infections caused by sexually transmitted bacteria or urinary pathogens frequently induce epididymo-orchitis, a primary contributor to male infertility. While standardized methodologies for ASA testing remain elusive, assisted reproductive treatments such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and intrauterine insemination (IUI) show promise in overcoming immune-mediated infertility. Conclusions: This review underscores the critical role of infection, inflammation, and autoimmune responses in male infertility. It highlights the necessity of improving diagnostic methods, understanding immune-pathological mechanisms, and addressing medicolegal issues associated with male infertility. This knowledge could pave the way for innovative therapies, ultimately enhancing fertility outcomes, and mitigating the societal and legal repercussions of infertility. Full article

The incidence of male reproductive cancers, including prostate, testicular, and penile cancers, has risen in recent years, raising important health concerns. Prostate cancer is the second leading cause of cancer-related mortality in men, while penile cancer, though rare, typically affects men over 60. Testicular cancer, with a lifetime risk of about 0.4% in men, is most common among adolescents and young adults, decreasing sharply after the age of 40. Traditional treatments include chemotherapy, radiation, surgery, and combinations thereof, but advancements in immunotherapy and monoclonal antibodies are showing promising results, particularly for genitourinary cancers. These therapies, targeting immune checkpoints and tumor-specific antigens, are gaining traction as effective alternatives for resistant cases. This review provides evidence-based recommendations on current and emerging immunotherapy and monoclonal antibody treatments for male reproductive cancers, highlighting future directions to optimize patient outcomes. Full article

Extracellular vesicles (EVs) are gaining recognition for their essential role in enhancing gamete quality and improving outcomes in assisted reproductive technologies. These nanosized particles, released by cells, carry proteins, lipids, and RNAs, facilitating critical cell communication and offering the potential to enhance gamete maturation and improve fertilization rates. Most research on males has concentrated on seminal plasma, a complex fluid produced by the testes and accessory glands vital in modulating sperm fertility potential. The components of seminal plasma significantly affect sperm functionality, embryo survival, and placental development, making this a prominent area of interest in reproductive biology. The EVs within seminal plasma contribute to maintaining sperm membrane stability, enhancing motility, and promoting capacitation, which may influence the female reproductive tract following mating. In females, EVs have been identified in both the follicular and uterine environments, where effective embryo–maternal communication is crucial. The oviduct epithelium supports gamete transport and early embryonic development, with EVs found in oviductal fluid playing a key role in reproductive processes. These EVs support the embryo’s growth in the nutrient-rich uterine environment. These important studies underscore the significant role of EVs in transporting essential molecular compounds to gametes and embryos, leading to an enhanced understanding and potential manipulation of reproductive processes. This review aims to summarize the current research on the benefits of EVs in gamete manipulation and embryo development, highlighting their promising implications for reproductive health. Full article