Ontogenesis of testicular function in humans.

The two major functions of the testis, steroidogenesis and gametogenesis, take place during fetal life. These two functions have been extensively studied in rodents and adult humans. However, their onset during fetal life is poorly documented in humans. In the first part of this work we presented both our experimental data and some data of literature concerning the development of the human fetal testis. In the second part of this article, using the organ culture system we previously developed, we have investigated the regulations or perturbations of fetal testis development both in rodent and human models. Our findings provide important insight into the potential role of exposure to environmental pollutants (physical factors, in particular ionizing radiation, cadmium and endocrine disruptors such as phthalates) during fetal testicular development and their potential deleterious effects on male fertility in adulthood. Our results highlight the specificity of the human model compared with rodent models

Effect of environmental and pharmaceutical exposures on fetal testis development and function:a systematic review of human experimental data

BACKGROUND: Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance.OBJECTIVE AND RATIONALE: The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis.SEARCH METHODS: For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including 'endocrine disruptor', 'human', 'fetal', 'testis', 'germ cells', 'testosterone' and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches.OUTCOMES: A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues.WIDER IMPLICATIONS: Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.</p

Alien Registration- Legueux, Angenard (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/28707/thumbnail.jp

Alien Registration- Legueux, Angenard (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/28707/thumbnail.jp

Variabilité architecturale du test chez le genre Collyrites (Echinoidea, Disasteroidea) au Jurassique moyen.

15 pagesL'évolution de l'architecture du test et en particulier celle du « complexe système apical–périprocte » chez le genre Collyrites (Echinoidea, Disasteroidea) est analysée pour les espèces des étages Bathonien et Callovien (Jurassique moyen) provenant de plusieurs localités du bassin de Paris. Le système apical du genre Collyrites est subdivisé en deux parties : (i) une partie antérieure, dénommée trivium, composée de quatre plaques génitales (1, 2, 3, 4) et de trois plaques ocellaires (II ; III ; IV) ; (ii) une partie postérieure, dénommée bivium, composée de deux plaques ocellaires (I, V) et d'une plaque génitale (5), sans gonopore et non fonctionnelle, entourant le périprocte. Le passage Bathonien–Callovien est marqué par une disjonction du bivium en deux sous-ensembles : les plaques ocellaires (I et V) d'une part, et le périprocte et la plaque génitale (5) d'autre part. La plaque génitale 5 qui a tendance à basculer dans le périprocte n'est pas toujours observable. Cette disjonction entre bivium et périprocte s'accompagne de modifications architecturales. L'architecture du trivium reste relativement stable pendant le Bathonien et le Callovien ; une plaque supplémentaire peut toutefois venir s'insérer dans le trivium. L'architecture du bivium est beaucoup plus variable, en rapport avec la séparation du périprocte et des plaques ocellaires. Au fur et à mesure qu'augmente la distance séparant le bivium du périprocte, des plaques supplémentaires, de plus en plus nombreuses, s'intercalent dans l'intervalle ainsi créé. Dans le même temps, la taille de ces plaques supplémentaires augmente de manière significative. De plus, quelques spécimens du Bathonien et du Callovien peuvent présenter une architecture apicale atypique avec une plaque génitale supplémentaire ou une plaque génitale comportant deux pores. Ces observations sont interprétées dans le cadre du modèle extraxial axial theory (EAT) : (i) le « squelette axial » est composé par les plaques ocellaires et celles des ambulacres et des interambulacres ; (ii) le « squelette extraxial » correspond aux plaques génitales, aux plaques supplémentaires et à celles qui entourent le périprocte. L'étude présentée montre que la majorité de la variabilité observée sur le bivium est liée à un fort développement du squelette extraxial entre le Bathonien et le Callovien alors que le squelette axial reste stable au cours de cette période

Integrative genomic analysis identifies the core transcriptional hallmarks of human hepatocellular carcinoma Running title: Transcriptional hallmarks of liver cancer

International audienceIntegrative genomics helped characterize molecular heterogeneity in hepatocellular carcinoma (HCC), leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here, we performed a meta-analysis of 15 independent datasets (n = 784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared with the surrounding nontumor tissue. In the HCC signature, upregulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer. Cancer Res; 76(21); 6374-81. ©2016 AACR