Titre : La place controversée de la gestation pour autrui en 2021 : des repères éthiques (in)discutables ?

International audienceAt the time of the revision of French bioethics law and of the disruption of the access to assisted reproductive technology, surrogacy challenges the ethical benchmarks of French legislators. Surrogacy is at the intersection of numerous issues, whether they are medical, social, psychological, legal, political or feminist, and thus it questions the motto of the French Republic « Liberty, Equality, Fraternity ». At the center of many debates, the access to parenthood gives rise to passions when it is enabled by surrogacy. So, it leads to consider other alternatives as uterus transplant or even adoption. This article debates, through the subject of surrogacy, the symbolic value of motherhood and the place of child desire in the French society. This article aims to survey the potential feminine and child vulnerability to which surrogacy could expose. In the light of collected and discussed data, we advocate for a legal framework of surrogacy in order to avoid a hypocrisy of recognition in which the French system is currently positioned and to avoid the drifts indirectly accepted by France outside of its borders. The analysis is simple and clear: refusing to regulate, it's choosing not to protect anyone.À l’heure de la révision de la loi de bioéthique française et du bouleversement de l’accès à la procréation médicalement assistée, la gestation pour autrui vient questionner les repères éthiques auxquels se rattachent les législateurs français. Au carrefour de nombreuses problématiques médicales, sociales, psychologiques, légales, politiques ou encore féministes, la gestation pour autrui interroge la devise française « liberté, égalité, fraternité ». Au cœur de nombreux débats, l’accès à la parentalité soulève les passions quand elle est permise par la gestation pour autrui, ce qui induit d’envisager d’autres alternatives comme la greffe d’utérus ou encore l’adoption. Cet article discute, à travers la gestation pour autrui, la valeur symbolique de la maternité et la place du désir d’enfant dans la société française. Il a également pour objet de sonder la vulnérabilité féminine et infantile à laquelle cette pratique pourrait exposer. Au regard des données collectées et discutées, nous plaidons pour un encadrement légal de la gestation pour autrui afin d’éviter une hypocrisie de reconnaissance dans laquelle se place actuellement le système français et d’empêcher les dérives que la France tolère tacitement en dehors de ses frontières. Le constat est simple : refuser d’encadrer, c’est choisir de ne protéger personne

Les myélinosomes : une nouvelle voie du contrôle de qualité des protéines

International audienceMaintenance of cell proteostasis relies on two degradation pathways: proteasome and autophagy. Here we describe a new proteostasis pathway avoiding degradation of abnormal proteins yet carrying them outside the cell using nanovesicles called myelinosomes. These myelinosomes are produced in pathological or stress situations in relation with genetic or environmental factors. Myelinosome vesicles are nano-sized multi-stacked membrane structures, resembling myelin sheath. It has recently been shown in two models of genetic diseases (Huntington's disease and cystic fibrosis) that myelinosomes are important for eliminating mutant proteins in an unusual secretory process, thus preventing their accumulation and aggregation in cells

L’anonymat du don de gamètes à l’heure des tests génétiques

National audienceDevelopment of genetic testing direct-to-consumer (DTC) for recreational purposes, although prohibited in France, is a real challenge to the current practice of gamete donation. Indeed, anonymity is a fundamental principle contributing to the ethics of donation. This principle is weakened due to the availability to the general public of these tests on the Internet. Several thousands of people are conceived by gamete donation worldwide, some of whom do not know how they were conceived. Gamete donors should be informed that their anonymity is no longer guaranteed, as they can be found by homologies of their DNA, or that of a parent or a child, potentially available in databases. Thus, adults conceived by gamete donation but not informed by their parents can discover their way of conception. Recipients of gamete donation should also be informed that their child's DNA will establish the biological discrepancy and they should be encouraged to disclose the conception to their child. Several countries now allow children conceived by donation to obtain donor's identity. In France, the Bioethics Law is currently being finalized and will now allow access to donor's identity for people conceived by gamete donation

Impact of Endocrine Disruptors upon Non-Genetic Inheritance

International audienceSimilar to environmental factors, EDCs (endocrine-disrupting chemicals) can influence gene expression without modifying the DNA sequence. It is commonly accepted that the transgenerational inheritance of parentally acquired traits is conveyed by epigenetic alterations also known as ``epimutations''. DNA methylation, acetylation, histone modification, RNA-mediated effects and extracellular vesicle effects are the mechanisms that have been described so far to be responsible for these epimutations. They may lead to the transgenerational inheritance of diverse phenotypes in the progeny when they occur in the germ cells of an affected individual. While EDC-induced health effects have dramatically increased over the past decade, limited effects on sperm epigenetics have been described. However, there has been a gain of interest in this issue in recent years. The gametes (sperm and oocyte) represent targets for EDCs and thus a route for environmentally induced changes over several generations. This review aims at providing an overview of the epigenetic mechanisms that might be implicated in this transgenerational inheritance

Comment je fais… une MIV ex vivo

National audienc

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

Autophagie et spermatozoïde

National audienceSpermiogenesis, the ultimate stage of spermatogenesis, is a process involving autophagy. At this stage, the acrosome is generated by vesicular fusion and most of the cytoplasm disappears. Autophagy, literally "eating oneself", allowing the elimination and replacement of proteins and nonfunctional organelles, ensures the recycling of cellular constituents and is a highly conserved cellular mechanism within eukaryotic cells. The machinery of autophagy is present in the spermatozoon, regulating the vitality and mobility of the cells. The environmental and behavioral impact on autophagy and the consequences on spermatogenesis are beginning to be studied. The purpose of this review is to synthesize current knowledge about autophagy in the mature male gamete

Extra-cellular vesicles of the male genital tract: new actors in male fertility?

International audienceExtracellular Vesicles (EVs) are membrane-limited particles containing proteins, lipids, metabolites and nucleic acids that are secreted by healthy and cancerous cells. These vesicles are very heterogeneous in size and content and mediate a variety of biological functions. Three subtypes of EV have been described in the male genital tract: microvesicles, myelinosomes and exosomes. Each type of EVs depends on the location of secretion such as the testis, prostate or epididymis. It has been shown that EVs can fuse together and deliver information to recipient cells, for example spermatozoa in the male genital tract. Cryo-electron microscopy remains the reference technique for determining EV morphology, but quantifying the absolute concentration of these EVs in biological fluids remains a challenge from a clinical point of view. The field of bio detection has considerably increased with the introduction of nanomaterials in biosensors and will provide a better understanding of the impact of these EVs. However, functional modifications of male gametes result from interactions with the components of the intraluminal fluid all along the genital tract and depend on the secretion and absorption of proteins and lipids from the local microenvironment. We cannot therefore exclude the possibility of epigenetic modulation of the information that will be transmitted to the embryo and therefore to the next generation via EVs

Vésicules extracellulaires du liquide folliculaire humain : marqueurs histologiques de la pathologie ovarienne ?

Congrès AM/CHEC 2023 2023-03-09 LilleNational audienc

Diversity of Extracellular Vesicles in Human Follicular Fluid: Morphological Analysis and Quantification

International audienceThe oocyte microenvironment constituted by the follicular fluid (FF) is a key for the optimal development of female gametes. Its composition reflects the physiological state of the ovarian follicle. The particularity of FF is to contain a huge diversity of extracellular vesicles specific to women, in the same way as seminal plasma in men. Here, we described and compared morphological aspects of broad subcategories of human FF-related Extracellular Vesicles (EVs). EVs participate in physiological and pathological processes and have potential applications in diagnostics or therapeutics. EVs isolated from FF are involved in different biological functions related to follicular growth, oocyte maturation, and embryo development. However, knowledge on the morphology of FF-derived EVs is limited, mainly due to their sub-micrometer size and to intrinsic limitations in methods applied for their characterization. The aim of this study was to provide a comprehensive morphological description of EVs from FF of healthy subjects and quantification. EVs separation was realized by centrifugation, with comparison of the EV yield obtained from differential centrifugation and one-step ultracentrifugation. Cryo-Transmission Electron Microscopy was used to reveal the morphology, size, and phenotype of EVs. Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) were used to quantify and analyze the size distribution for each centrifugation step. We performed a comprehensive inventory of human follicular fluid EVs. We show that human FF contains a huge diversity of EVs. This study brings novel insights on EVs from normal FF and provides a reference for further studies of EVs in ovarian diseases