Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION: This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS: Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE: We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION: While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
ISSN: 0268-1161

inserm-00814146
http://www.hal.inserm.fr/inserm-00814146
DOI : 10.1093/humrep/des360
PUBMED : 23024119

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The NW-trending Talas-Ferghana Fault (TFF) in Kyrgyzstan, Central Asia, is one of the largest intracontinental strike-slip faults in the world. It extends over a distance of more than 2000 km from southern Tourghai to western Tarim and exhibits a maximum dextral offset of ∼200 km during the late Palaeozoic to present. The history of the fault provides important insights for the understanding of the evolution of southern Central Asia but remains poorly constrained due to lack of reliable geochronological data. We present new Ar-Ar ages and structural data from the Kyrgyz West Tianshan, that elucidate the kinematic history of the TFF in the Palaeozoic and Mesozoic. 40Ar/39Ar ages on mylonitic white micas document a deformational history consisting of several episodes. A late Carboniferous age of 312 ± 4 Ma point to initiation of top-to-the-south and dextral transpressional deformation during a metamorphic overprint in Precambrian and Palaeozoic rocks along the northern compartment of the TFF. The main phase of dextral motion along the entire fault occurred in the Permian as suggested by minimum ages of 260-290 Ma obtained at two different locations in the NW and central parts of the TFF. Partial isotopic resetting occurred between 240 and 210 Ma and younger ages of <200-210 Ma are ascribed to late brittle reactivation and hydrothermal fluid flow in the Late Triassic to Early Jurassic times. The Jurassic trans-tensional phase is featured by emplacement of 195 ± 3 Ma pegmatitic dykes. The Ar-Ar mineral ages and structural data argue for a major phase of dextral shearing, affecting the entire region from the West Tianshan to Mongolia in the late Permian and leading to formation of almost equally spaced major NW-trending dextral strike-slip faults. The uniform character of this deformation indicates that the process of amalgamation in this part of the CAOB ended prior to the late Permian, and Central Asia evolved as a single coherent continental block since that time.
ISSN: 0743-9547

hal-00831326
https://hal.archives-ouvertes.fr/hal-00831326
DOI : 10.1016/j.jseaes.2013.02.012

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The Nile delta sedimentation constitutes a continuous high resolution (1.6 mm/year) record of Ethiopian African monsoon regime intensity. Multiproxy analyses performed on core MS27PT recovered in hemipelagic Nile sediment margin (<90 km outward of the Rosetta mouth of the Nile) allow the quantification of the Saharan aeolian dust and the Blue/White Nile River suspended matter frequency fluctuations during the last 21 cal. ka BP. The radiogenic Sr and Nd isotopes, clay mineralogy, bulk elemental composition and palynological analyses reveal large changes in source components, oscillating between a dominant aeolian Saharan contribution during the LGM and the Late Holocene (~4 to 2 cal. ka BP), a dominant Blue/Atbara Nile River contribution during the early Holocene (15 to 8.4 cal. ka BP) and a probable White Nile River contribution during the Middle Holocene (8.4 to 4 cal. ka BP). The following main features are highlighted: 1. The rapid shift from the LGM arid conditions to the African Humid Period (AHP) started at about 15 cal. ka BP. AHP extends until 8.4 cal. ka BP, and we suggest that the Ethiopian African Monsoon maximum between 12 and 8 cal. ka BP is responsible for a larger Blue/Atbara Nile sediment load and freshwater input into the Eastern Mediterranean Sea. 2. The transition between the AHP and the arid Late Holocene is gradual and occurs in two main phases between 8.4 and 6.5 cal. ka BP and 6.5 to 3.2 cal. ka BP. We suggest that the main rain belt shifted southward from 8.4 to ~4 cal. ka BP and was responsible for progressively reduced sediment load and freshwater input into the eastern Mediterranean Sea. 3. The aridification along the Nile catchments occurred from ~4 to 2 cal. ka BP. A dry period, which culminates at 3.2 cal. ka BP, and seems to coincide with a re-establishment of increased oceanic primary productivity in the western Mediterranean Sea. We postulate that the decrease in thermo-haline water Mediterranean circulation could be part of a response to huge volumes of fresh-water delivered principally by the Nile River from 12 to 8.4 cal. ka BP in the eastern Mediterranean. We propose that the large hydrological change in Ethiopian latitude could be a trigger for the 8.2 ka cooling event recorded in high latitude. Revel R., Colin C., Bernasconi S., Combourieu-Nebout N., Ducassou E., Grousset F.E., Rolland Y., Migeon S., Brunet P., Zhaa Y., Bosch D., Mascle J.,. "21,000 years of Ethiopian African moonsoon variability recorded in sediments of the western Nile deep sea fan", Regional Environmental Change,
ISSN: 1436-3798

hal-00836300
https://hal.archives-ouvertes.fr/hal-00836300

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.
ISSN: 1553-7390

hal-01063929
https://hal.archives-ouvertes.fr/hal-01063929
DOI : 10.1371/journal.pgen.1004340
PUBMED : 24784881

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A dense, local network of 30 geodetic markers covering a 50 × 60 km2 area in the southwestern European Alps (Briançon region) has been temporarily surveyed in 1996, 2006 and 2011 by GPS. The aim is to measure the current deformation in this seismically active area. The study zone is characterized by a majority of extensional and dextral focal mechanisms, along north–south to N160 oriented faults. The combined analysis of the three measurement campaigns over 15 years and up to 16 years of permanent GPS data from the French RENAG network now enables to assess horizontal velocities below 1 mm/year within the local network. The long observation interval and the redundancy of the dense campaign network measurement help to constrain a significant local deformation pattern in the Briançon region, yielding an average E–W extension of 16 ± 11 nanostrain/year. We compare the geodetic deformation field to the seismic deformation rate cumulated over 37 years, and obtain good coherencies both in amplitude and direction. Moreover, the horizontal deformation localized in the Briançon region represents a major part of the Adriatic-European relative plate motion. However, the average uplift of the network in an extensional setting needs the presence of buoyancy forces in addition to plate tectonics.
ISSN: 0264-3707

hal-01119724
https://hal.archives-ouvertes.fr/hal-01119724
DOI : 10.1016/j.jog.2015.02.001

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Growth charts are an essential clinical tool for evaluating a child's health and development. The current French reference curves, published in 1979, have recently been challenged by the 2006 World Health Organization (WHO) growth charts. To evaluate and compare the growth of French children who were born between 1981 and 2007, with the WHO growth charts and the French reference curves currently used. Anthropometric measurements from French children, who participated in 12 studies, were analyzed: 82,151 measurements were available for 27,257 children in different age groups, from birth to 18 years. We calculated and graphically compared mean z-scores based on the WHO and French curves, for height, weight and Body Mass Index (BMI) according to age and sex. The prevalence of overweight using the WHO, the French and International Obesity Task Force definitions were compared. Our population of children was on average 0.5 standard deviations taller than the French reference population, from the first month of life until puberty age. Mean z-scores for height, weight and BMI were closer to zero based on the WHO growth charts than on the French references from infancy until late adolescence, except during the first six months. These differences not related to breastfeeding rates. As expected, the prevalence of overweight depended on the reference used, and differences varied according to age. The WHO growth charts may be appropriate for monitoring growth of French children, as the growth patterns in our large population of French children were closer to the WHO growth charts than to the French reference curves, from 6 months onwards. However, there were some limitations in the use of these WHO growth charts, and further investigation is needed.
ISSN: 1932-6203

hal-01134193
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134193
DOI : 10.1371/journal.pone.0120806
PUBMED : 25761138
PUBMEDCENTRAL : PMC4356547

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The geologic evolution of the South Armenian Block (SAB) in the Mesozoic is reconstructed from a structural, metamorphic, and geochronologic study including U–Pb and 40Ar/39Ar dating. The South Armenian Block Crystalline Basement (SABCB) outcrops solely in a narrow tectonic window, NW of Yerevan. The study of this zone provides key and unprecedented information concerning closing of the Northern Neotethys oceanic domain north of the Taurides-Anatolides platform from the Middle Jurassic to the Early Cretaceous. The basement comprises of presumed Proterozoic orthogneiss overlain by metamorphosed pelites as well as intrusions of granodiorite and leucogranite during the Late Jurassic and Early Cretaceous. Structural, geochronological and petrological observations show a multiphased evolution of the northern margin of the SAB during the Late Jurassic and Early Cretaceous. A south-dipping subduction under the East Anatolian Platform-South Armenian Block (EAP-SAB) is proposed in order to suit recent findings pertaining emplacement of relatively hot subduction related granodiorite as well as the metamorphic evolution of the crystalline basement in the Lesser Caucasus area. The metamorphism is interpreted as evidencing: (1) M1 Barrovian MP–MT conditions (staurolite–kyanite) at c. 157–160 Ma and intrusion of dioritic magmas at c. 150–156 Ma, (2) near-adiabatic decompression is featured by partial melting and production of leucogranites at c. 153 Ma, followed by M2 HT–LP conditions (andalusite–K-feldspar). A phase of shearing and recrystallization is ascribed to doming at c. 130–150 Ma and cooling at 400 °C by c. 123 Ma (M3). Structural observations show (1) top to the north shearing during M1 and (2) radial extension during M2. The extensional event ends by emplacement of a thick detrital series along radial S, E and W-dipping normal faults. Further, the crystalline basement is unconformably covered by Upper Cretaceous-Paleocene series dated by nannofossils, evolving from Maastrichtian marly sandstones to Paleocene limestones.
ISSN: 0743-9547

hal-01174077
https://hal.archives-ouvertes.fr/hal-01174077
DOI : 10.1016/j.jseaes.2014.07.018

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow â €' early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. © The Author(s) 2017.
ISSN: 2045-2322

hal-01517095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01517095
DOI : 10.1038/srep44184
PUBMED : 28281692

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and DA) are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both NA and DA contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection.
ISSN: 0737-4038

hal-01578587
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587/file/J%C3%A9gou%20et%20al%20-%20Meiotic%20Genes%20Are%20Enriched.pdf
DOI : 10.1093/molbev/msx141

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
We report the development of the ReproGenomics Viewer (RGV), a multi-and cross-species working environment for the visualization, mining and comparison of published omics data sets for the reproductive science community. The system currently embeds 15 published data sets related to gametogenesis from nine model organisms. Data sets have been curated and conveniently organized into broad categories including biological topics, technologies, species and publications. RGV's modular design for both organisms and genomic tools enables users to upload and compare their data with that from the data sets embedded in the system in a cross-species manner. The RGV is freely available at http://rgv.genouest.org.
ISSN: 0305-1048

hal-01146120
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146120
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146120/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146120/file/nar.gkv345.full.pdf
PUBMED : 25883147

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
U-Pb zircon and Ar-Ar amphibole and biotite ages from rocks of the West Congo Belt of Angola indicate that this area underwent two main deformation events of amphibolite facies grade at c. 540 and 490 Ma, which were followed by tectonically assisted exhumation during eastward thrusting of the hinterland domain onto the foreland domain. High-grade conditions in the West Congo Belt are 20-40 Ma younger than in the Ribeira-Araçuai Belt of Brazil, its South American counterpart, or than in the westernmost Kaoko Belt of Namibia, its African correlative. In the present state of knowledge, a more appropriate counterpart to the southern part of the West Congo Belt may be restricted to the Cabo Frio Terrane in the eastern Ribeira Belt, which yields a broadly similar evolution.
ISSN: 0954-4879

hal-00716463
https://hal.archives-ouvertes.fr/hal-00716463
DOI : 10.1111/j.1365-3121.2012.01060.x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The continental South Armenian Block – part of the Anatolide–Tauride South Armenian microplate – of Gondwana origin rifted from the African margin after the Triassic and collided with the Eurasian margin after the Late Cretaceous. During the Late Cretaceous, two northward dipping subduction zones were simultaneously active in the northern Neo-Tethys between the South Armenian Block in the south and the Eurasian margin in the north: oceanic subduction took place below the continental Eurasian margin and intra-oceanic subduction resulted in ophiolite obduction onto the South Armenian Block in the Late Cretaceous.The paleolatitude position of the South Armenian Block before its collision with Eurasia within paleogeographic reconstructions is poorly determined and limited to one study. This earlier study places the South Armenian Block at the African margin in the Early Jurassic. To reconstruct the paleolatitude history of the South Armenian Block, we sampled Upper Devonian–Permian and Cretaceous sedimentary rocks in Armenia. The sampled Paleozoic rocks have likely been remagnetized. Results from two out of three sites sampled in Upper Cretaceous strata pass fold tests and probably all three carry a primary paleomagnetic signal. The sampled sedimentary rocks were potentially affected by inclination shallowing. Therefore, two sites that consist of a large number of samples (> 100) were corrected for inclination shallowing using the elongation/inclination method.These are the first paleomagnetic data that quantify the South Armenian Block's position in the Tethys ocean between post-Triassic rifting from the African margin and post-Cretaceous collision with Eurasia. A locality sampled in Lower Campanian Eurasian margin sedimentary rocks and corrected for inclination shallowing, confirms that the corresponding paleolatitude falls on the Eurasian paleolatitude curve. The north–south distance between the South Armenian Block and the Eurasian margin just after Coniacian–Santonian ophiolite obduction was at most 1000 km.
ISSN: 0040-1951

hal-01365871
https://hal.archives-ouvertes.fr/hal-01365871
DOI : 10.1016/j.tecto.2015.01.012