Epididymis Response Partly Compensates for Spermatozoa Oxidative Defects in snGPx4 and GPx5 Double Mutant Mice

We report here that spermatozoa of mice lacking both the sperm nucleaus glutathione peroxidase 4 (snGPx4) and the epididymal glutathione peroxidase 5 (GPx5) activities display sperm nucleus structural abnormalities including delayed and defective nuclear compaction, nuclear instability and DNA damage. We show that to counteract the GPx activity losses, the epididymis of the double KO animals mounted an antioxydant response resulting in a strong increase in the global H2O2-scavenger activity especially in the cauda epididymis. Quantitative RT-PCR data show that together with the up-regulation of epididymal scavengers (of the thioredoxin/peroxiredoxin system as well as glutathione-S-transferases) the epididymis of double mutant animals increased the expression of several disulfide isomerases in an attempt to recover normal disulfide-bridging activity. Despite these compensatory mechanisms cauda-stored spermatozoa of double mutant animals show high levels of DNA oxidation, increased fragmentation and greater susceptibility to nuclear decondensation. Nevertheless, the enzymatic epididymal salvage response is sufficient to maintain full fertility of double KO males whatever their age, crossed with young WT female mice

L’analyse automatisée du sperme, l’andrologie 2.0

International audienceThere are mainly two automatic spermiology technologies, CASA (Computer-Assisted Semen Analysis) and SQA (Sperm Quality Analyser). Automatons save time and provide standardized and reproducible evaluation of sperm concentration and motility. However, they remain to be perfected for morphology analysis. To date, they allow rapid screening of altered versus normozoospermic sperm, but cannot replace a trained technician and the manual analysis. In parallel, semen analysis systems on smartphones or using kits are now freely available. They are inexpensive and feasible at home and allow an initial estimate of presence of spermatozoa before medical care. Artificial intelligence systems with autonomous learning "machinelearning" are also being developed to improve the characterization of sperm, including the choice of gamete to be injected in ICSI (Intra Cytoplasmic Sperm Injection).Il existe deux technologies principales d’automates de spermiologie, les CASA et les SQA. Ces automates permettent un gain de temps et l’évaluation standardisée et reproductible de la concentration et de la mobilité des spermatozoïdes. Cependant, ils restent à être perfectionnés pour l'analyse de la morphologie. A ce jour, s’ils autorisent un dépistage rapide des spermes, ils ne peuvent pas remplacer un technicien formé et une analyse manuelle. En parallèle, des systèmes d'analyse de sperme sur smartphones ou utilisant des kits sont désormais disponibles en accès libre. Ils sont peu coûteux, réalisables chez soi et donnent une première estimation de la présence de spermatozoïdes avant une prise en charge médicale. Des systèmes d'intelligence artificielle avec apprentissage autonome («machine-learning») sont également en cours de développement et permettent d'améliorer la caractérisation des spermatozoïdes, y compris dans le choix du gamète à injecter en ICSI

Computer-assisted semen analysis

International audienceComputer-assisted semen analysis (CASA) systems are equipment that use different methodologies. When a laboratory wishes to acquire these systems, it is important to know how they perform. CASA has been “relegated” to the “advanced semen examinations” section in the latest version of the World Health Organization (WHO) lab manual because there is a lack of literature to demonstrate its full utility in routine infertility diagnosis. However, some systems perform very well in assessing sperm motility and sperm count. In the context of assisted reproductive techniques (ARTs), these systems save time and can provide a standardized assessment of the characteristics of semen prepared for ART. CASA systems are evolving steadily, artificial (AI) systems are being developed, and smartphone-based sperm analysis systems are now available for home analysis. It is clear that andrology and ART are rapidly changing fields, whereas AI and automation are only just beginning. But in a few years’ time, there is no doubt that these CASA systems should improve further and enable what the WHO manual has been calling for since 2010: greater reproducibility and standardization

Induced Pluripotent Stem Cells in Drug Discovery and Neurodegenerative Disease Modelling

Induced pluripotent stem cells (iPSCs) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and much attention has been given to developing iPSC-based disease models to validate drug discovery platforms and study the pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and unique properties. Moreover, iPSCs can differentiate into multiple cell types. These are essential characteristics, since the study of neurological diseases is affected by the limited access to injury sites, the need for in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, the challenges of postmortem cell culture, and ethical issues. Neurodegenerative diseases strongly impact global health due to their high incidence, symptom severity, and lack of effective therapies. Recently, analyses using disease specific, iPSC-based models confirmed the efficacy of these models for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modelling and drug testing, with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases

[Cryoconservation of gametes: how to perform?]

International audienceCryoconservation of gametes : how to perform ? The patients can preserve their gametes when they are exposed to potential gonadotoxic pathology or treatment. In this context, the French bioethical law clearly states the obligation to inform the patients about the risks for their fertility and the possibilities to cryopreserve their gametes. Regional platforms of fertility preservation allow notably for the coordination of the oncology teams and the CECOS. For the men, sperm freezing is achieved by a slow and controlled temperature protocol. For the women, the oocytes are usually vitrified after hormonal stimulation and ovarian punction. For both, the gametes are cryopreserved in straws and stored in liquid nitrogen until use in assisted reproductive treatment (ART). Each year, the CECOS keeping the gametes interrogates patients on their wish to continue, or not, the cryoconservation. The gametes can only be used in ART by the patients only during their lifetime and with their consent, without alterations related to the duration of storage

Impact du stress oxidant sur la qualité nucléaire spermatique

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Impact of slow freezing on sperm nuclear quality and telomere length

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La supplémentation en hypotaurine des milieux de préparation et de congélation améliore la qualité fonctionnelle et nucléaire spermatique

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Détection de la maladie résiduelle du sarcome d’Ewing dans le tissu ovarien et testiculaire par une méthode sensible et spécifique

International audienc

Détection de la maladie résiduelle du sarcome d’Ewing dans le tissu ovarien et testiculaire par une méthode sensible et spécifique

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