Dynamics of the transcriptional landscape during human fetal testis and ovary development

Acknowledgements We thank all members of the SEQanswers forums for helpful advice; Steven Salzberg and Cole Trapnell for continuous support with the ‘Tuxedo’ suite; and the UCSC Genome team members. Sequencing was performed by the GenomEast platform, a member of the ‘France Génomique’ consortium (ANR-10-INBS-0009). We thank Ms Linda Robertson, Ms Margaret Fraser, Ms Samantha Flannigan (University of Aberdeen) and the staff at Grampian NHS Pregnancy Counselling Service and all the staff of the Department of Obstetrics and Gynecology of the Rennes Sud Hospital for their expert assistance and help, and the participating women, without whom this study would not have been possible. The authors are grateful for Ms Gersende Lacombe and Mr Laurent Deleurme from the Biosit CytomeTri cytometry core facility of Rennes 1 University. Funding French National Institute of Health and Medical Research (Inserm); University of Rennes 1; French School of Public Health (EHESP); Swiss National Science Foundation [SNF n° CRS115_171007 to B.J.]; the French National Research Agency [ANR n° 16-CE14-0017-02 and n°18-CE14-0038-02 to F.C]; Medical Research Council [MR/L010011/1 to PAF]; European Community’s Seventh Framework Programme (FP7/2007–2013) [under grant agreement no 212885 to PAF]; European Union’s Horizon 2020 Research and Innovation Programme [under grant agreement no 825100 to P.A.F. and S.M.G.].Peer reviewedPostprin

Glutathion S-Transferase genetic polymorphisms modify the effect of exposure to solvents during pregnancy on risk of birth defects

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Proteomic Analysis of Efferent Ducts: Identification of Potential Biomarkers and Targets of Endocrine Disruptors

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Dynamics of the transcriptional landscape during human gonad development from fetal to adulthood

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Proteome analysis and genome-wide regulatory motif prediction identify novel potentially sex-hormone regulated proteins in rat efferent ducts.

International audienceThe efferent ducts are a series of tubules that conduct sperm from the rete testis to the epididymis. They absorb most fluid and proteins originating from the rete testis during concentration of spermatozoa prior to their entry into the epididymis. Proteome analysis of micro-dissected efferent duct samples from adult rats was combined with genome-wide computational prediction of conserved hormone response elements to identify factors likely regulated by oestrogens and androgens. We identified 165 proteins and found subsets of the promoters controlling their corresponding genes to contain androgen- and oestrogen response elements (ARE/EREs) at similar frequencies. Moreover, EREs were significantly enriched among the loci identified compared with their genome-wide occurrence. The expression and localization of Anxa6, Ckb, Krt19, Park7, Pdzk1 and Tpt1 in the efferent ducts and other related hormone controlled tissues was further validated at the RNA or protein level. This study identifies many novel proteins predicted to play roles in sperm maturation and male fertility and provides significant computational evidence that the efferent ducts express genes transcriptionally controlled by sex hormones

Profil protéomique des canaux efférents : identification de protéines potentiellement régulées par les stéroïdes sexuels, androgènes et œstrogènes.

The efferent ducts are a series of tubules that conduct sperm from the rete testis to the epididymis. They are involved in the reabsorption of the bulk of fluid and proteins originating from the rete testis during concentration of spermatozoa prior to their entry into the epididymis. In the present investigation, we have applied proteomics and bioinformatics to identify proteins that are expressed in the efferent ducts from adult rats, putatively regulated by estrogens and androgens. This approach has allowed the identification of a first set of proteins, among which an important proportion have one or more estrogen responsive elements (ERE) and/or androgen responsive elements (ARE) in their putative promoter. Furthermore, supporting evidence of such regulation is reported in the literature for many of these protein candidates. Additionally, the validation of efferent duct expression for several newly described proteins was performed. Finally, using state-of-the-art mass spectrometry imaging techniques, we have identified several new proteins whose expression appears to be specific to efferent ducts. Their characterization is presently undergoing in our laboratory. Our findings extend the present knowledge of efferent duct biology and reinforce the concept that efferent duct structure and function are under significant control by both estrogens and androgens. Ultimately, these findings point out possible targets of xenosteroids in the male genital tract

Dynamics of the transcriptional landscape during human gonad development from fetal to adulthood

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The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes.

International audienceSelenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues