المؤلفون: Geoffroy-Siraudin, Cendrine, Perrard, Marie-Hélène, Chaspoul, Florence, Lanteaume, André, Gallice, Philippe, Durand, Philippe, Guichaoua, Marie-Roberte

مصطلحات موضوعية: REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY

الوصف: There is evidence that exposure to environmental factors is at least partly responsible for changes in semen quality observed over the past decades. The detection of reproductive toxicants under Registration, Evaluation and Authorisation of Chemicals (REACH) will impact animal use for regulatory safety testing. We first validated a model of culture of rat seminiferous tubules for toxicological studies on spermatogenesis. Then, using this model of culture, we assessed the deleterious effects of 1, 10, and 100 μg/l hexavalent chromium [Cr(VI)] on meiotic cells. The prophase I of meiosis was studied in vivo and ex vivo . Bromo-2′-deoxyuridine (BrdU) was used to describe the kinetics of germ cell differentiation. SCP3 labeling allowed to establish the distribution of the stages of the meiotic prophase I and to perform a qualitative study of the pachytene stage in the absence or presence of Cr(VI). The development of the meiotic step of pubertal rats was similar in vivo and ex vivo . The number of total cells appeared not affected by the presence of Cr(VI) irrespective of its concentration. However, the numbers of late spermatocytes and of round spermatids were decreased by Cr(VI) even at the lower concentration. The percentage of synaptonemal complex abnormalities increased slightly with the time of culture and dramatically with Cr(VI) concentrations. This model of culture appears suitable for toxicological studies. This study shows that Cr(VI) is toxic for meiotic cells even at low concentrations, and its toxicity increases in a dose-dependent manner.

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العلاقة: http://toxsci.oxfordjournals.org/cgi/content/short/116/1/286Test; http://dx.doi.org/10.1093/toxsci/kfq099Test

الإتاحة: https://doi.org/10.1093/toxsci/kfq099Test
http://toxsci.oxfordjournals.org/cgi/content/short/116/1/286Test

المؤلفون: Longepied, Guy, Saut, Noemie, Aknin-Seifer, Isabelle, Levy, Rachel, Frances, Anne-Marie, Metzler-Guillemain, Catherine, Guichaoua, Marie-Roberte, Mitchell, Michael J.

مصطلحات موضوعية: Reproductive genetics

الوصف: BACKGROUND Deletion of the entire AZFb interval from the Y chromosome is strictly associated with azoospermia arising from maturation arrest during meiosis. Here, we describe the exceptional case of an oligozoospermic man, 13-1217, with an AZFb + c (P5/distal-P1) deletion. Through the characterization of this patient, and two AZFb (P5/proximal-P1) patients with maturation arrest, we have explored three possible explanations for his exceptionally progressive spermatogenesis. METHODS AND RESULTS We have determined the precise breakpoints of the deletion in 13-1217, and shown that 13-1217 is deleted for more AZFb material than one of the AZFb -deleted men (13-5349). Immunocytochemical analysis of spermatocytes with an antibody against a synaptonemal complex component indicates synapsis to be largely unaffected in 13-1217, in contrast to 13-5349 where extended asynapsis is frequent. Using PCR-based analyses of RNA and DNA from the same testicular biopsy, we show that 13-1217 expresses post-meiotic germ cell markers in the absence of genomic DNA and transcripts from the AZFb and AZFc intervals. We have determined the Y chromosome haplogroup of 13-1217 to be HgL-M185. CONCLUSIONS Our results indicate that the post-meiotic spermatogenesis in 13-1217 is not a consequence of mosaicism or retention of a key AZFb gene. On the contrary, since the Hg-L Y chromosome carried by 13-1217 is uncommon in Western Europe, a Y-linked modifier locus remains a possible explanation for the oligozoospermia observed in patient 13-1217. Further cases must now be studied to understand how germ cells complete spermatogenesis in the absence of the AZFb interval.

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العلاقة: http://humrep.oxfordjournals.org/cgi/content/short/25/10/2655Test; http://dx.doi.org/10.1093/humrep/deq209Test

الإتاحة: https://doi.org/10.1093/humrep/deq209Test
http://humrep.oxfordjournals.org/cgi/content/short/25/10/2655Test

المؤلفون: Dieterich, Klaus, Zouari, Raoudha, Harbuz, Radu, Vialard, François, Martinez, Delphine, Bellayou, Hanane, Prisant, Nadia, Zoghmar, Abdelali, Guichaoua, Marie Roberte, Koscinski, Isabelle, Kharouf, Mahmoud, Noruzinia, Mehrdad, Nadifi, Sellama, Sefiani, Abdelaziz, Lornage, Jacqueline, Zahi, Mohamed, Viville, Stéphane, Sèle, Bernard, Jouk, Pierre-Simon, Jacob, Marie-Christine, Escalier, Denise, Nikas, Yorgos, Hennebicq, Sylviane, Lunardi, Joël, Ray, Pierre F.

مصطلحات موضوعية: Article

الوصف: Infertility concerns a minimum of 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. In a previous study we demonstrated that a homozygous mutation (c.144delC) in the Aurora Kinase C ( AURKC ) gene led to the production of large-headed polyploid multi-flagellar spermatozoa, a primary infertility phenotype mainly observed in North Africans. We now want to estimate the prevalence of the defect, to improve our understanding of AURKC physiopathology in spermatogenesis and assess its implication in oogenesis. A carrier frequency of 1/50 was established from individuals from the Maghrebian general population, comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. A total of 62 patients were genotyped, all who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n=32) while no AURKC mutations were detected in the others. Two homozygous females were identified; both were fertile indicating that AURKC is not indispensible in oogenesis. Previous FISH results had showed a great chromosomal heterogeneity in these patient's spermatozoa. We demonstrate here by flow cytometry that all spermatozoa have in fact a homogeneous 4C DNA content and are thus all blocked before the first meiotic division. Our data thus indicate that a functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis.

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العلاقة: http://hmg.oxfordjournals.org/cgi/content/short/ddp029v1Test; http://dx.doi.org/10.1093/hmg/ddp029Test

الإتاحة: https://doi.org/10.1093/hmg/ddp029Test
http://hmg.oxfordjournals.org/cgi/content/short/ddp029v1Test