title: In vivo notch signaling blockade induces abnormal spermatogenesis in the mouse.
abstract: In a previous study we identified active Notch signaling in key cellular events occurring at adult spermatogenesis. In this study, we evaluated the function of Notch signaling in spermatogenesis through the effects of in vivo Notch blockade. Adult CD1 male mice were either submitted to a long term DAPT (?-secretase inhibitor) or vehicle treatment. Treatment duration was designed to attain one half the time (25 days) or the time (43 days) required to accomplish a complete cycle of spermatogenesis. Blockade of Notch signaling was depicted from decreased transcription of Notch effector genes. Notch signaling blockade disrupted the expression patterns of Notch components in the testis, induced male germ cell fate aberrations, and significantly increased germ cell apoptosis, mainly in the last stages of the spermatogenic cycle, and epididymis spermatozoa morphological defects. These effects were more pronounced following the 43 day than the 25 day DAPT treatment schedule. These results indicate a relevant regulatory role of Notch signaling in mammalian spermatogenesis.
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Murta
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Batista
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Gulbenkian Institute of Science, Oeiras, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Trindade
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Silva
authors.affiliation: Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Henrique
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Gulbenkian Institute of Science, Oeiras, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Duarte
authors.affiliation: Reproduction and Development, Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Lopes-da-Costa
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects*; D000072056:Transcription Factor HES-1
chemical_list: D053829:Amyloid Precursor Protein Secretases; D051792:Basic Helix-Loop-Helix Proteins; D004151:Dipeptides; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C499040:Nrarp protein, mouse