Sperm DNA methylation dynamics after chemotherapy: a longitudinal study of a patient with testicular germ cell tumor treatment

International audienceBACKGROUND: An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring. OBJECTIVES: Here, we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to 2 years after a bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: A TGCT was diagnosed in a 30-year-old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12, and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs). RESULTS: The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development. DISCUSSION AND CONCLUSION: The consequences of the cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages

Versatile SOG/SU-8/fluorinated SU-8 rib optical waveguides as microsystems: single-mode TE00-TM00 straight waveguides, S-bends, Y-junctions, Mach-Zehnder interferometers

International audienc

Le VIH-1, un lentivirus au potentiel d’endogénisation dans la lignée germinale humaine ?

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Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV

International audienceViruses have colonized the germ line of our ancestors at several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few non-retroviruses. Among the recently emerged viruses infecting humans, several target the testis (eg HIV, Zika and Ebola viruses). 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 <i>in vitro</i> 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 SIV DNA were detected within a few TGCs in the testis from one infected patient, one rhesus macaque and one African Green monkey <i>in vivo</i> Molecular landscape analysis revealed that early TGCs were enriched in HIV early co-factors up to integration and had overall low antiviral defenses when 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 our germline and become endogenous in the future, as happened during human evolution for a number of viruses.<b>IMPORTANCE</b> Viruses have colonized the host germ line at 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 <i>in vitro</i> Our results indicate that isolated primary TGCs express alternative HIV-1 receptors allowing virions binding but not entry. However, HIV-1 entered and integrated in TGCs upon cell-associated infection, and produced low level of viral proteins. <i>In vivo,</i> 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 the future generations

Les SHS et les questions environnementales, manières de voir, manières de faire

Services écosystémiques, biodiversité, risques naturels, ressources naturelles, vulnérabilité ou encore résilience, autant de dispositifs de qualification de ce que l’on nomme communément « l’environnement » qui donnent à voir la diversité des enjeux écologiques et politiques identifiés par les sociétés et notamment les scientifiques. Les questions environnementales se trouvent ainsi au carrefour des dynamiques écologiques, sociales et politiques. Les sciences jouent un rôle important dans la construction même de ces questions. Si l’on saisit facilement l’implication des sciences de l’univers et des techniques, les SHS elles aussi sont concernées. Elles sont, en effet, régulièrement sollicitées pour produire de l’expertise support d’aide à la décision. Ainsi, appréhender les questions liées à environnement nécessite des approches transversales tant différents champs interviennent dans la construction des relations (représentations/pratiques/régulations) à l’environnement – écologique, politique, symbolique, technique – mais aussi des postures réflexives. Cette livraison de Sciences de la Société contribue à éclairer la façon selon laquelle les chercheurs appréhendent ces questions environnementales danstrois registres principaux : comment les contextes sociaux, économiques, institutionnels, politiques, disciplinaires, pèsent-ils sur leur choix ? Quels liens existent entre les approches théoriques, les problématiques, les méthodes et les outils conceptuels ? Comment ajuste-t-on, combine-t-on des cadres cohérents pour produire des connaissances scientifiques et quelles sont les portées et limites des choix effectués

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study

International audienceBackground: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19.Methods: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis.Results: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state.Conclusion: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders

Effects of azithromycin and doxycycline on the vaginal microbiota of women with urogenital Chlamydia trachomatis infection: a substudy of the Chlazidoxy randomized controlled trial

Objectives: Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and doxycycline on the vaginal microbiota in a cohort of women with a urogenital C. trachomatis infection randomly assigned to one of these treatments (Chlazidoxy trial). Methods: We analysed vaginal samples from 284 women (135 in the azithromycin group and 149 in the doxycycline group) collected at baseline and 6 weeks after treatment initiation. The vaginal microbiota was characterized using 16S rRNA gene sequencing and classified into community state types (CSTs). Results: At baseline, 75% (212/284) of the women had a high-risk microbiota (CST-III or CST-IV). A crosssectional comparison 6 weeks after treatment showed that 15 phylotypes were differentially abundant, but this difference was not reflected at the CST (p 0.772) or diversity level (p 0.339). Between baseline and the 6-week visit, a-diversity (p 0.140) and transition probabilities between CSTs were not significantly different between the groups, and no phylotype was differentially abundant. Discussion: In women with urogenital C. trachomatis infection, the vaginal microbiota does not seem to be affected by azithromycin or doxycycline 6 weeks after treatment. Because the vaginal microbiota remains susceptible to C. trachomatis infection (with CST-III or CST-IV) after antibiotic treatment, women remain at risk of reinfection, which could originate from unprotected sexual intercourse or untreated anorectal C. trachomatis infection. This last consideration advocates for the use of doxycycline instead of azithromycin because of its higher anorectal microbiological cure rate. Jeanne Tamarelle, Clin Microbiol Infect 2023;29:1056 & COPY; 2023 European Society of Clinical Microbiology and Infectious Diseases.Plateforme d'Innovation " Forêt-Bois-Fibre-Biomasse du Futur