The toxicity of superparamagnetic iron oxide nanoparticles induced on the testicular cells: In vitro study.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.

Stem cell therapy for erectile dysfunction: a systematic review.

INTRODUCTION: Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and neurologic factors. Existing treatments for ED mainly focus on symptom relief rather than addressing the underlying cause. Stem cells (SCs) have shown potential as a therapeutic approach for ED due to their anti-inflammatory properties. OBJECTIVES: This systematic review aims to assess the current status of trials and determine the potential impact of SCs on male sexual health. METHODS: A comprehensive search strategy was employed to gather relevant articles from 6 electronic databases. The search included articles published until March 2023. The reference lists of articles were manually reviewed to identify additional studies of relevance. The eligibility criteria for inclusion in the analysis focused on clinical trials involving humans that evaluated the safety and efficacy of SC therapy for ED. Exclusion criteria encompassed case reports, case series, abstracts, reviews, and editorials, as well as studies involving animals or SC derivatives. Data extraction was performed via a standardized form with a focus on erectile outcomes. RESULTS: A total of 2847 articles were initially identified; 18 were included in the final analysis. These studies involved 373 patients with ED and various underlying medical conditions. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs. CONCLUSION: SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.

High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients.

BACKGROUND: Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis. RESULTS: We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA's presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient's infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. CONCLUSIONS: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.

Motherhood after breast cancer: can we balance fertility preservation and cancer treatment? A narrative review of the literature.

Breast cancer may affect young women who have not yet completed childbearing. Assisted reproductive technology (ART) provides alternatives for fertility preservation such as oocyte, embryo or ovarian tissue cryopreservation. We reviewed the published literature on fertility-preserving management in breast cancer, aiming at finding evidence to answer the following questions: (1) What are the fertility sparing options available?; (2) How do these women respond to IVF? and (3) Can pregnancy influence breast cancer recurrence? There is a paucity of publications describing clinical experience and outcome data which limits accessibility to fertility preservation in this setting. Presently, oocyte or embryo cryopreservation are the main options for fertility preservation. IVF success rates are comparable to the ones of non-oncological populations according to the woman's age but current published studies lack data on definitive success rates following embryo banking for cancer patients. The perception that IVF and pregnancy may worsen cancer prognosis remains, despite the lack of scientific evidence to support this notion. Published studies show reassuring results for pregnancies occurring >2 years after breast cancer diagnosis. The best published evidence suggests pregnancy after breast cancer does not increase the risk of disease recurrence, thus pregnancy should not be forbidden once treatment is completed. Decision making for women diagnosed with cancer requires up-to-date knowledge of the efficacy and safety of available options. Providing consultation with a reproductive specialist and appropriate information on fertility preservation for these women should be an essential aspect of their supportive care.