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Today many heterosexual couples, as well as single women and lesbian couples, use gamete donation in France or abroad in order to fulfil their desire for a child. The construction of parenthood in these conditions raises many questions and requires specific psychological work in order to reflect on issues surrounding genetic transmission, the establishment of the bond and the appropriation of parenthood. Furthermore, what is the future of the children conceived by donation?, (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

It was a strong and long-standing demand of people born of gamete donation: to know who is the person who allowed them to come into the world. The French legislator seemed to take this need into account during the last revision of the bioethics law. But if the rules have already changed for donors, for whom anonymity becomes fixed-term, for individuals born from a donation, access to their origins is far from being guaranteed to this day., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Most of transgender people plan to have a family but their fertility may be affected by gender affirmation. Hormone therapy can permanently affect gamete production, especially in trans women. Sex reassignment surgery leads to permanent sterility. In France, networks of health professionals have been organized and recommend access to fertility preservation for trans people. However, gamete collection is often difficult due to hormonal incongruence for trans women or to the invasive nature of the procedure for trans men. Future studies are required to assess the use of self-preserved gametes by trans people., (© 2022 médecine/sciences – Inserm.)

French law lies down a principle of anonymity of donated gametes. This principle is ignored by English law. Moreover, English law has established, few years ago, the contrary principle: the one of transparency of the donor's identity. This study of English law reports this evolution and its consequences.

Medical taking part in procreation in gamete and embryo donation is recent in France and has been included in the field of medically assisted procreation as defined by a law since 1994. Theses activities are strictly regulated. If procreation using donor sperm has been broadly carried out for 30 years in the CECOS leading to the birth of approximately 40,000 children, oocyte and embryo donation had a more recent and limited development. The main questions to which are faced the couples procreating through gamete and embryo donation is whether their child should be told about its origin since they have to build a parenthood and a filiation which are not first depending on biological and genetic links.

Dinoflagellates from the globally distributed genus Alexandrium are known to produce both paralytic shellfish toxins (PST) and uncharacterized bioactive extracellular compounds (BEC) with allelopathic, ichthyotoxic, hemolytic and cytotoxic activities. In France, blooms of Alexandrium minutum appear generally during the spawning period of most bivalves. These blooms could therefore alter gametes and/or larval development of bivalves, causing severe issues for ecologically and economically important species, such as the Pacific oyster Crassostrea (=Magallana) gigas. The aim of this work was to test the effects of three strains of A. minutum producing either only PST, only BEC, or both PST and BEC upon oyster gametes, and potential consequences on fertilization success. Oocytes and spermatozoa were exposed in vitro for 2 h to a range of environmentally realistic A. minutum concentrations (10-2.5 × 10 4  cells mL -1 ). Following exposure, gamete viability and reactive oxygen species (ROS) production were assessed by flow cytometry, spermatozoa motility and fertilization capacities of both spermatozoa and oocytes were analysed by microscopy. Viability and fertilization capacity of spermatozoa and oocytes were drastically reduced following exposure to 2.5 × 10 4  cells mL -1 of A. minutum. The BEC-producing strain was the most potent strain decreasing spermatozoa motility, increasing ROS production of oocytes, and decreasing fertilization, from the concentration of 2.5 × 10 3  cells mL -1 . This study highlights the significant cellular toxicity of the BEC produced by A. minutum on oyster gametes. Physical contact between gametes and motile thecate A. minutum cells may also contribute to alter oyster gamete integrity. These results suggest that oyster gametes exposure to A. minutum blooms could affect oyster fertility and reproduction success., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

DEVILLE J.-L., GRAVIS G., SALEM N., SAVOIE P.-H., ESTERNI B., WALZ J., THOMAS P., GONCALVES A., VIENS P. & BLADOU F. (2010) European Journal of Cancer Care 19, 827-832 Resection of residual masses after chemotherapy for advanced non-seminomatous germ cell tumours, a monocentric analysis of pre-operative prognosticators Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells ( P= 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P= 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P= 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres. [ABSTRACT FROM AUTHOR]

Development 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., (Copyright © 2020. Published by Elsevier Masson SAS.)

Harmful algal blooms (HABs) of toxic species of the dinoflagellate genus Dinophysis are a threat to human health as they are mainly responsible for diarrheic shellfish poisoning (DSP) in the consumers of contaminated shellfish. Such contamination leads to shellfish farm closures causing major economic and social issues. The direct effects of numerous HAB species have been demonstrated on adult bivalves, whereas the effects on critical early life stages remain relatively unexplored. The present study aimed to determine the in vitro effects of either cultivated strains of D. sacculus and D. acuminata isolated from France or their associated toxins (i.e. okadaic acid (OA) and pectenotoxin 2 (PTX2)) on the quality of the gametes of the Pacific oyster Crassostrea gigas. This was performed by assessing the ROS production and viability of the gametes using flow cytometry, and fertilization success using microscopic counts. Oocytes were more affected than spermatozoa and their mortality and ROS production increased in the presence of D. sacculus and PTX2, respectively. A decrease in fertilization success was observed at concentrations as low as 0.5 cell mL -1 of Dinophysis spp. and 5 nM of PTX2, whereas no effect of OA could be observed. The effect on fertilization success was higher when both gamete types were concomitantly exposed compared to separate exposures, suggesting a synergistic effect. Our results also suggest that the effects could be due to cell-to-cell contact. These results highlight a potential effect of Dinophysis spp. and PTX2 on reproduction and recruitment of the Pacific oyster., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this study was to describe the incidence, clinical and histological characteristics, treatment and long-term follow-up of bilateral germ-cell tumours (BGCT) of the testis in order to determine in what respects they differ significantly from unilateral germ-cell tumours. In all, 31 patients with BGCT had metachronous tumours and 14 had synchronous tumours. Among the metachronous tumours, 61% occurred more than 5 years after the first tumour. The overall incidence of BGCT in patients with testicular germ-cell tumours (TGCT) was 1.9%. The incidence was 3.2% in patients presenting with a seminoma and 1.4 % in patients presenting with a nonseminomatous germ-cell tumour (NSGCT). Patients under 30 years of age at the time of the initial diagnosis had a higher incidence of bilateral tumours compared with older men. The outcome of BGCT was excellent. A high association was found between BGCT, sterility and suspected genetic risk factors for TGCT. These results argue against a systematic contralateral biopsy at diagnosis of first TGCT in all patients, but emphasise the importance of patient education and of the need to better identify patients at risk for a second TGCT. Therapeutic indications for synchronous BGCT, including conservative treatment, need to be better defined.British Journal of Cancer (2004) 90, 55-59. doi:10.1038/sj.bjc.6601464 www.bjcancer.com [ABSTRACT FROM AUTHOR]

The current conditions of gamete donation in france. Law of bioethics and assisted reproductive technology legislation control gamete donation in France. Candidates for the gamete donation are still too few to date, not allowing to meet the needs of couples receiving gametes on French territory. This shortage leads to significant waiting times for these couples. The information provided to the candidates of gamete donation (oocytes and spermatozoa) is channeled through general practitioners as foreseen by the law. A good knowledge of recruitment rules for candidates and of the attribution conditions of the gamete donations allows the practitioners to disseminate the information and to support the recruitment of new candidates., Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

The article discusses the "Oocyte maturation and fertilization: lessons from canonical and emerging models" workshop held at the Oceanologic Observatory of Banyuls in France in June 2013 and was organized by researchers Anne-Marie Geneviere, Olivier Haccard, Peter Lenart and Alex McDougall. It highlights the research reports presented by researchers in the meeting on various topics such as germline formation, oocyte development, sperm, fertilization and early development.

Introduction CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC. Methods and results We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC. Discussion Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' instead of HDGC. [ABSTRACT FROM AUTHOR]

Viral gametocytic hypertrophy was reported for the first time in 2001 in Pacific oyster Crassostrea gigas in France. Since this date, the number of reported cases and the distribution area have increased every year; however, the cases are not associated with macroscopic signs or increased mortality rates. Both male and female gametes were hypertrophied and basophilic inclusions were observed in gamete nuclei. Transmission electron microscopy revealed the presence of viral particles in these intranuclear basophilic inclusions. These particles had characteristics similar to those of the Papillomaviridae and Polyoma viridae families: they were small, non-enveloped, icosahedral, and 44 to 56 nm in diameter. The viral particles were found in male, female and hermaphrodite oysters and no significant difference in viral infection was observed between those groups. The frequency of detection and the intensity of infection were low and no host defence reaction was recognised, suggesting that the viral particles had a weak impact on C. gigas. The viral particles described in the present study seem to be similar to these described in C. virginica in the USA and Canada and in C. gigas in Korea, but further studies are required to confirm their identity. The issue of a possible emergence of this infection is discussed.

Abstract  In recent decades, testicular cancer incidence has considerably increased in a majority of industrialized countries. In France, short reports suggested that the testicular cancer incidence rate has also risen, especially in north-eastern regions. In Europe, geographical variation of incidence rates has been observed in Baltic countries and a clear birth cohort effect has been revealed. This study aimed to assess temporal trends in testicular cancer incidence in southern France. We examined incidence rates over a 20-year time period in a series of 506 consecutive cases of testicular cancer recorded from 1980 to 1999 in the Midi-Pyrenees region of France. Age, calendar period, and birth cohort effects were examined simultaneously using Poisson regression models. Our analysis found a significant rise in the overall incidence rate of testicular germ cell tumors from 1.27 to 3.04 per 100,000 between 1980–1984 and 1995–1999, an annual increase of 5.70%. These results, the first obtained in a large series in southern Europe, show a twofold increase in incidence rate of testicular cancer in the Midi-Pyrenees region, which is very similar to that observed in all European countries, more or less doubling in the last 20 years. Interestingly, this major jump and the apparent testicular cancer gradient between northern and southern Europe suggest considerable geographical heterogeneity in incidence, but low geographical variation in temporal trends. [ABSTRACT FROM AUTHOR]

Y chromosome microdeletion screening is advised in cases of severely impaired spermatogenesis. Improvements in molecular biological techniques have made diagnosis more accessible in routine analysis. However, Y chromosome microdeletions are not diagnosed in all IVF centres. The aim of the present study was to determine the regulatory (indications, financing) and performance (methods, invoicing) conditions required for this analysis, in France. Microdeletion detection was found to be spreading fast and consistantly. It therefore seems necessary for a consensus to be reached on indications, with a view to a standardized technique, with a common effort of experts in the field. Financial management by the French Health Insurance bodies (Sécurité Sociale) would be an essential step towards routine adoption. Lastly, the answers to our questionnaire revealed a strong demand for information concerning this analysis. [ABSTRACT FROM AUTHOR]

Understanding how abiotic factors influence the spatial distribution of genetic variation provides insight into microevolutionary processes. The intertidal seascape is characterized by highly heterogeneous habitats which probably influence the partitioning of genetic variation at very small scales. The effects of tidal height on genetic variation in both the haploid (gametophytes) and diploid (tetrasporophytes) stages of the red alga Chondrus crispus were studied. Fronds were sampled every 25 cm within a 5 m × 5 m grid and along a 90-m transect at two shore heights (high and low) in one intertidal site in France. The multilocus genotype of 799 fronds was determined (Nhaploid  = 586; Ndiploid  = 213) using eight microsatellite loci to test the following hypotheses: (i) high and low shore fronds belong to genetically differentiated populations, (ii) gene flow is restricted within the high shore habitat due to tidal-influenced isolation and (iii) significant FIS values are driven by life history characteristics. Pairwise FST estimates between high and low shore levels supported the hypothesis that high and low shore fronds were genetically differentiated. The high shore was characterized by the occurrence of within-shore genetic differentiation, reduced genetic diversity and increased levels of intergametophytic selfing, suggesting it is a marginal environment. These results suggest at fine scales within the intertidal seascape the same mechanisms as those over the species' distributional range are at work with core and marginal population dynamics., (© 2013 John Wiley & Sons Ltd.)

Epidemiological studies on intracranial tumors have suggested that the observed familial aggregation of a proportion of gliomas may be due to inherited predisposition to their development. In the Li-Fraumeni syndrome (LFS) associated with germ-line mutations of the p53 gene, nervous-system tumors are observed with increased frequency. However, the contribution of germ-line p53 mutation to the incidence of brain tumors has not been investigated. In order to address this point, we have performed 2 independent investigations. First, we have examined an unselected series of brain tumors. Whenever the presence of a p53 mutation in the tumor was observed, the possible germ-line origin of the mutation was investigated. Germ-line p53 mutations were also analyzed in constitutional DNA of patients with gliomas that had been selected for an unusual personal or familial history of cancer. Germ-line p53 mutations were detected in 1 out of 80 unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ-line p53 mutation may contribute to a small fraction of gliomas that develop in the general population. The presence of a personal or familial history of cancer in a patient with glioma should prompt the search for a germ-line p53 mutation. However, the low frequency of p53 germ-line mutation suggests that alterations of this gene may not account for most familial cases of gliomas.

Background: Despite several diagnostic guidelines, Fetal Alcohol Spectrum Disorders (FASDs) remain underdiagnosed or misdiagnosed, delaying the care of these patients and support for families. Objective: This study aims to help professionals caring for these children and their families to suspect this diagnosis earlier and to provide the most appropriate follow-up. Methods: A retrospective chart review with monocentric recruitment was performed at the Genetics Unit of the University Hospital of Reunion Island. A total of 147 children and adolescents with FASDs were included. Results: Prenatal alcohol exposure was associated with paternal alcohol consumption in 42.9%, and a high rate of prematurity (33.3%) was observed. Sixty percent of children or adolescents were placed in foster families. Learning difficulties without cognitive deficits were found in 65.8% of cases (50/76). Postural control and fine motor skills disabilities were described, respectively, in 54.7% (35/64) and 72.5% (50/69) of cases. A systematic genetic assessment was carried out, identifying in these FASD patients an associated Copy Number Variation (CNVs) in 22.6% of cases. Conclusion: Children with FASDs combine significant vulnerabilities, associating exposure to alcohol during the preconception and/or the prenatal period, prematurity, complex familial and sociocultural living conditions, and a genetic anomaly in almost a quarter of cases. [ABSTRACT FROM AUTHOR]

Objective: To localize the different proteins involved in the executioner step of apoptosis in the human testicular tissue: effector caspases (3, 6, and 7), caspase inhibitors called inhibitor of apoptosis proteins (IAPs, such as XIAP), and IAP inhibitors such as Smac/DIABLO and to investigate XIAP and Smac expression and activation of caspase-3 in azoospermia. Design: Retrospective study. Setting: The Biology of Reproduction Center of Poissy and Inserm U407, France. Patient(s): Twenty-five patients diagnosed as azoospermic and 4 patients with normal testicular histology. Intervention(s): Testicular biopsies for histopathological assessment. Main Outcome Measure(s): Localization of proteins by immunohistochemistry. Result(s): Effector caspase-7 seemed to be absent from normal human testes, whereas procaspase-3 and procaspase-6 were detected in both somatic and germ cells. XIAP was mainly expressed in Sertoli cells, whereas its inhibitor Smac was detected in pachytene spermatocytes. On the other hand, although few apoptotic germ cells were detected in biopsies from patients with obstructive azoospermia, increased levels of apoptotic germ cells were detected in spermatogenetic arrest. This increase in apoptotic germ cells was associated with increased levels of active caspase-3 in patients with spermatogenetic arrest, whereas the expression of XIAP and Smac/DIABLO was at similar levels in all groups. Conclusion(s): Active caspase-3 might be important in the apoptotic process observed in spermatogenetic arrest. [Copyright &y& Elsevier]

Abstract: Many chromosomal abnormalities have been reported to date in pigs. Most of them have been balanced structural rearrangements, especially reciprocal translocations. A few cases of XY/XX chimerism have also been diagnosed within the national systematic chromosomal control program of young purebred boars carried out in France. Until now, this kind of chromosomal abnormality has been mainly reported in intersex individuals. We investigated 38,XY/38,XX boars presenting apparently normal phenotypes to evaluate the potential effects of this particular chromosomal constitution on their reproductive performance. To do this, we analyzed (1) the chromosomal constitution of cells from different organs in one boar; (2) the aneuploidy rates for chromosomes X, Y, and 13 in sperm nuclei sampled from seven XY/XX boars. 2n = 38,XX cells were identified in different nonhematopoietic tissues including testis (frequency, <8%). Similar aneuploidy rates were observed in the sperm nuclei of XY/XX and normal individuals (controls). Altogether, these results suggest that the presence of XX cells had no or only a very limited effect on the reproduction abilities of the analyzed boars. [Copyright &y& Elsevier]

Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS. [ABSTRACT FROM AUTHOR]

The IFRG meeting 2010 was held in the beautiful city of Tours in France. The topics now reported included the storage and early embryo development; new developments in incubation temperature; and the influence of glucose application to poultry embryos. Two aspects of cryopreservation were considered: primordial germ cells, and in vivo cryopreserved cock semen. The latter was tested to assess its feasibility for use in commercial production or preservation of genetic stocks. With regard to commercial poultry production, the data recorded in one study supported the hypothesis that fertility would be higher and would persist for longer in pens where the birds were able to find a physical refuge from other birds. Other factors affecting the production of turkeys, ducks, pheasants, ostriches, chickens and ducks were discussed, thus fulfilling the meeting's objective of reporting research into the incubation and fertility of all avian species. [ABSTRACT FROM AUTHOR]

The Jacques Monod Conference on 'Growth and regeneration during development and aging' was organized by Claude Desplan and Allison Bardin in May 2023. The conference took place in Roscoff, France, where participants shared recent conceptual advances under the general motto that developmental processes do not end with embryogenesis. The meeting covered various aspects of how development relates to fitness, regeneration and aging across a refreshing diversity of evolutionarily distant organisms. [ABSTRACT FROM AUTHOR]

Fatty acids and carotenoids are known to have roles in embryonic and larval development of sea cucumbers, but their changes in gonads during gametogenesis have not yet been studied. To improve our knowledge of the reproductive cycle of sea cucumbers in an aquaculture perspective, we collected 6–11 individuals of the species Holothuria (Panningothuria) forskali Delle Chiaje, 1823 approximately every 2 months from December 2019 to July 2021 east of the Glenan Islands (Brittany – France; 47.710°N, 3.948°W) at a depth of 8–12 m. Our results show that soon after spawning, sea cucumbers take advantage of an increased food availability in spring to rapidly and opportunistically accumulate nutrients in the form of lipids in their gonads (from May to July) and then slowly elongate, desaturate and probably rearrange fatty acids within lipid classes for the next reproductive season according to the specific requirements of both sexes. In contrast, acquisition of carotenoids occurs synchronously with gonads filling and/or through the reabsorption of spent tubules (T5), thus revealing little seasonal variations at the scale of the entire gonad in terms of relative abundance in both sexes. All results suggest that gonads are fully replenished with nutrients by October and that broodstock for induced reproduction could be captured at this moment and kept until the production of larvae is required. Maintaining broodstock for consecutive years would probably be a higher level challenge as the dynamics of tubule recruitment are not fully understood and seem to last for several years. [ABSTRACT FROM AUTHOR]

Simple Summary: Testicular cancer is the most common cancer among men below 40 years old, and its causes remain largely unknown. Marked geographic differences in the occurrence along with the relatively young age at diagnosis suggest a possible role of environmental and occupational exposures that occur early in life, probably already during embryonic development. Using data from a French case–control study, we investigated associations between paternal occupational exposure to five heavy metals and welding fumes before and at birth and testicular cancer risk in sons. We estimated exposures from job titles and considered other potential risk factors in the statistical analyses. We found no association. Thus, further research is necessary to identify potentially modifiable risk factors. Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case–control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons. [ABSTRACT FROM AUTHOR]

Simple Summary: Adolescents and young adults (AYA) with cancer often fall through gaps between children's and adults' cancer services. They are consequently under-represented in clinical trials, and their survival is often inferior to that of children or adults with the same tumor type; in this paper, we use the example of central nervous system germ cell tumors (CNS-GCT), as a model of AYA tumor to illustrate this challenge. We describe how we have built bridges between pediatric and adult oncology, how this can apply to other types of brain tumors, and discuss ways to promote cancer care in the AYA population. Adolescents and young adults (AYA) with cancer are under-represented in clinical trials and have thus not benefited from the same improvement in outcomes as either younger or older patients. Central nervous system germ cell tumors (CNS-GCT) represent an ideal model of AYA tumor as their incidence peaks during adolescence and young adulthood. Since the early 90's, SIOP (International Society of Pediatric Oncology) has launched two successive European trials: SIOP CNS-GCT96 (January 1996 to December 2005) and SIOP CNS-GCTII protocols (October 2011 to July 2018), for CNSGCTs. With the removal of the upper age limit in the SIOP CNS-GCTII trial, and closer collaboration between pediatric and adult oncologists within AYA multidisciplinary tumor boards, the proportion of adults enrolled in France has dramatically increased over time. The current article will use the example of CNS-GCT to illustrate how to build a bridge between pediatric and adult oncology, how this can apply to other types of brain tumors, and how to promote cancer care in the AYA population. [ABSTRACT FROM AUTHOR]

Since the Nobel Prize award more than twenty years ago for discovering the core apoptotic pathway in C. elegans, apoptosis and various other forms of regulated cell death have been thoroughly characterized by researchers around the world. Although many aspects of regulated cell death still remain to be elucidated in specific cell subtypes and disease conditions, many predicted that research into cell death was inexorably reaching a plateau. However, this was not the case since the last decade saw a multitude of cell death modalities being described, while harnessing their therapeutic potential reached clinical use in certain cases. In line with keeping research into cell death alive, francophone researchers from several institutions in France and Belgium established the French Cell Death Research Network (FCDRN). The research conducted by FCDRN is at the leading edge of emerging topics such as non-apoptotic functions of apoptotic effectors, paracrine effects of cell death, novel canonical and non-canonical mechanisms to induce apoptosis in cell death-resistant cancer cells or regulated forms of necrosis and the associated immunogenic response. Collectively, these various lines of research all emerged from the study of apoptosis and in the next few years will increase the mechanistic knowledge into regulated cell death and how to harness it for therapy. [ABSTRACT FROM AUTHOR]

Featured Application: The characteristics of X-rays generated at the synchrotron facilities in Australia (the Australian Synchrotron) and France (the European Synchrotron Radiation Facility) share common features which provide the basis for development of new modalities for cancer radiotherapy treatment. In addition to the empirical optimization of the physical configurations of the radiation, research is now focused on the underlying radiobiological mechanisms, especially in the context of systemic "non-targeted effects". Studies have been conducted at synchrotron facilities in Europe and Australia to explore a variety of applications of synchrotron X-rays in medicine and biology. We discuss the major technical aspects of the synchrotron irradiation setups, paying specific attention to the Australian Synchrotron (AS) and the European Synchrotron Radiation Facility (ESRF) as those best configured for a wide range of biomedical research involving animals and future cancer patients. Due to ultra-high dose rates, treatment doses can be delivered within milliseconds, abiding by FLASH radiotherapy principles. In addition, a homogeneous radiation field can be spatially fractionated into a geometric pattern called microbeam radiotherapy (MRT); a coplanar array of thin beams of microscopic dimensions. Both are clinically promising radiotherapy modalities because they trigger a cascade of biological effects that improve tumor control, while increasing normal tissue tolerance compared to conventional radiation. Synchrotrons can deliver high doses to a very small volume with low beam divergence, thus facilitating the study of non-targeted effects of these novel radiation modalities in both in-vitro and in-vivo models. Non-targeted radiation effects studied at the AS and ESRF include monitoring cell–cell communication after partial irradiation of a cell population (radiation-induced bystander effect, RIBE), the response of tissues outside the irradiated field (radiation-induced abscopal effect, RIAE), and the influence of irradiated animals on non-irradiated ones in close proximity (inter-animal RIBE). Here we provide a summary of these experiments and perspectives on their implications for non-targeted effects in biomedical fields. [ABSTRACT FROM AUTHOR]

Background: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development.Methods: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression.Results: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype.Conclusions: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted. [ABSTRACT FROM AUTHOR]

Recently, research has contributed to better knowledge on the occurrence of pesticides in coastal water by identifying frequently detected substances, their concentration range and their acute and chronic toxicity for organisms. Pesticide pollution is of particular concern in France due to important agricultural activities and presence of several exoreic catchment areas that vehicle pesticides up to coastal waters, impacting non-target marine species. Several ecotoxicology questions remain to be addressed concerning the long-term effects of chronic pesticide exposure and the mechanisms involved in adaptation to chemical stress. In the present study, we brought new insights on the genetic and epigenetic effects of the herbicide diuron in oyster genitors. During gametogenesis, we exposed Crassostrea gigas to environmentally realistic herbicide concentrations (0.2–0.3 μg L−1 during two 7-day periods at half-course and end of gametogenesis). Diuron exposure was shown to decrease global DNA methylation and total methyltransferase activity in whole oyster tissue; this is consistent with the previous observation of a significant decrease in DNMT1 gene expression. Diuron effect seemed to be tissue-specific; hypermethylation was detected in the digestive gland, whereas diuron exposure had no effect on gill and gonad tissue. The genotoxicity of diuron was confirmed by the detection of one adduct in gonad DNA. By using in vitro approaches and human DNMT1 (DNMT1 has not been purified yet in bivalves), the presence of DNA lesions (adduct, 8-oxodGuo) was shown to interfere with DNMT1 activity, indicating a complex interaction between DNA damage and DNA methylation. Based on our results, we propose mechanisms to explain the effect of diuron exposure on DNA methylation, a widespread epigenetic mark. [ABSTRACT FROM AUTHOR]

Background European directives stipulate that French employers take all available measures to reduce the use of carcinogenic, mutagenic, and reprotoxic (CMR) chemicals. Our study explores the trends for the various control measures that are available to employees exposed to CMR agents, at two time points (2003 and 2010). Methods Our study assessed data from the 2003 and the 2010 French national cross-sectional survey of occupational hazards (SUMER). The availability of collective protections (source-based controls and general ventilation) and personal protective equipment (PPE) was explored. Trends in the availability of protective measures were studied using multilevel logistic regressions. Results Exposure situations without any protective measures decreased considerably between 2003 and 2010 (29.9% versus 17.9%, respectively). The increase in the proportion of exposure situations involving source-based controls (e.g. an isolation chamber and local exhaust ventilation) was, however, much less. Multiple regression analysis showed that the protection strategies depended on the job characteristics (e.g. work schedules, the employment contract, and the occupation) as well as the size of the company. There were noticeable changes between 2003 and 2010. For example, differences in protections available between full-time and part-time workers disappeared in the 7-year period, whereas those between executives/managers and other employees increased, as did the gaps between large and small companies. Conclusions Although the overall increase in exposure situations involving protective measures masks a number of differences in exposure between employee categories, it is a step in the right direction. Source-based controls appeared to be implemented more for exposures with the longest durations, and PPE was very often combined with collective protections, which is what is currently recommended. [ABSTRACT FROM AUTHOR]

A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p =.007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p =.031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system. The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress. [ABSTRACT FROM AUTHOR]

Background: To explore trends in social and occupational inequalities in terms of exposure to carcinogenic, mutagenic and reprotoxic chemicals (CMR) for French employees. Methods: Our study assessed data from the French national cross-sectional survey of occupational hazards (SUMER) that was conducted in 2003 and 2010. We included all of the 27 CMR agents that were classified by the International Agency for Research on Cancer or European Union regulations as being known or presumed to have CMR potential in humans. Trends in prevalence and degree of exposure were examined using multilevel logistic regression analysis. Results: The number of employees exposed to CMR agents decreased by 17.5% between 2003 and 2010. The only CMR entities for which exposure rates increased are not considered to be proven CMRs according to the European Union regulations. With the exception of apprentices, there was an overall decrease in exposure prevalence for all employees. This decrease occurred, however, to different extents. The decrease in the risk of exposure to CMR agents was much greater for those on permanent contracts, managers, and in enterprises with more than 500 employees. Nonetheless, in situations where there was potential for exposure, companies with fewer than 10 employees were in fact able to decrease the degree of risk more than the others. Conclusions: Our results confirm the relevance of reinforcing regulatory restrictions for CMR products, while also indicating that monitoring of trends in disparities will allow public health policy makers to better evaluate progress made toward reducing disparities that affect vulnerable populations. [ABSTRACT FROM AUTHOR]

Purpose: To explore varied exposure to carcinogenic, mutagenic, and reprotoxic chemicals (CMR) for French employees. Methods: Our study assessed data from the French national cross-sectional survey of occupational risks (SUMER) that was conducted in 2010 in a national representative sample of employees. We selected 28 CMR agents that were classified by the International Agency for Research on Cancer or European Union as being known or presumed to have CMR potential in humans. The association of individual and job characteristics with exposure prevalence, duration, and intensity of the CMR agents during a 1-week period was examined using multilevel logistic regression analysis. Results: Overall, 10.4% of employees in 2010 were exposed to one or more CMR agents at their workplace, and 3.4% were subjected to multiple CMR exposures. Blue-collar workers, night-shift workers and workers with short-term employment contracts experienced higher exposure prevalence ( p < 0.01) and intensity ( p < 0.05). Blue-collar workers and shift workers experienced also longer exposure duration ( p < 0.001). Conversely, managers, workers of large companies, and women were less exposed to CMR agents ( p < 0.001). The presence of a Committee for Health, Safety, and Working Conditions, and intervention by Occupational Health and Safety officers were significantly associated with reduced exposure intensities ( p < 0.001 and p < 0.05). Establishment of European CMR regulations and the existence of an applicable substitution principle reduced the exposure duration ( p < 0.001) and intensity ( p < 0.05). Conclusions: Our results point out disparities in CMR exposure and identify high-priority targets for prevention measures to help reducing social health discrepancies. [ABSTRACT FROM AUTHOR]

Discharges of saline effluents into rivers can lead to risks for local aquatic ecosystems. A specific ecological risk assessment methodology has been developed to propose a management tool to organisations responsible for managing rivers and industrial companies producing saline effluents. This methodology involves the detailed description of the spatiotemporal system concerned, the choice of ecological targets to be preserved, and the performance of bioassays adapted to each of the compartments of the river. Following development, it was applied to an industrial effluent in eastern France. For the scenario studied, results obtained suggest a high risk for the organisms of the water column and a low risk for the organisms of the periphyton. This difference can be explained by the structure of the latter which integrate extracellular polymers secreted by the organisms of the biofilm, forming a gel with a porous structure that acts as a barrier to diffusion. The methodology formulated permitted identifying the critical points of the spatiotemporal system studied and then using them as the basis for making well-grounded proposals for management. Lastly, proposals to improve the methodology itself are made, especially concerning the integration of the sediment compartment in the version formulated initially. [ABSTRACT FROM AUTHOR]

The common whelk Buccinum undatum (Neogastropoda, Buccinidae) is widespread along the north Atlantic coasts of France. In west Cotentin (Normandy), an important local fishery exists that depends exclusively on this marine resource and represents about 90% of French whelk production. Despite successive restrictive measures, fishing yields have decreased since 2000. Shell length frequency distributions of Buccinum undatum caught in west Cotentin were studied in 2005 (N = 2910), in 2007 (N = 2032) and in 2009 (N = 4145) ranging from 7 to 85 mm. In order to preserve this fishery and to characterise the whelk stock at this site, the reproductive biology of this species was studied in relation to age, sex and size, for whelks of commercial size (45 to 61 mm) over the complete annual cycle in 2008. Age was determined by reading the number of operculum striae: animals between 45 and 59 mm had 2 to 4 striae. Four reproductive stages were defined for males and females on the basis of histological analysis. The time course of reproductive events was described according to size and sex: the highest percentages of ripe stages were found in October for both sexes. Spawning events occurred between October and December. The shell length that corresponded to 50% of animals having mature gonads (49 mm and 52 mm for males and females, respectively, corresponding to 3 and 4 years old animals) exceeded the minimal landing size (45 mm). Fifty percent maturity was reached for males in their third year and for females in their fourth year. Reproductive investment was evaluated by quantitative analysis of the gonadal thickness or surface and was found to be proportional to shell size. We found that less than 20% of females under 49 mm in length were sexually mature and that these produced only a few eggs. This information, collected in a major fishing area, should assist fishery management decisions. [ABSTRACT FROM PUBLISHER]

A new homoscleromorph sponge species was observed for the first time in 2002 along the coast of Provence (France) and since then, several investigations have been implemented. The new homoscleromorph species is devoid of skeleton and it is thus related to the Oscarella genus. Oscarella balibaloi sp. nov. has been found in several littoral submarine caves of the Western Mediterranean Sea (France and Spain). After several years of monitoring, we show that this sponge is becoming abundant in several locations. The species has a peculiar habit, often overgrowing massive sponges, gorgonians or some erected bryozoans. Oscarella balibaloi sp. nov. is thinly encrusting, with an irregular morphology, lobate surface, and soft and very slimy consistency. Its color is white to orange. At the cytological level, this new species is characterized by three distinct types of cells with inclusions in its mesohyl: one with vacuoles and the others with paracrystalline inclusions. The reproduction pattern is very similar to other Oscarella species. We also present a specific metabolic fingerprint and compare it to that of other Mediterranean Oscarella species. [ABSTRACT FROM AUTHOR]