In vivo notch signaling blockade induces abnormal spermatogenesis in the mouse

• Published in: PloS one 2014-11, Vol.9 (11), p.e113365-e113365
• Main Authors: Murta, Daniel, Batista, Marta, Trindade, Alexandre, Silva, Elisabete, Henrique, Domingos, Duarte, António, Lopes-da-Costa, Luís
• Format: Article
• Language: English
• Subjects: Aberration; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Animals; Apoptosis; Apoptosis - drug effects; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biology and Life Sciences; Cell fate; Defects; Dipeptides - pharmacology; Drug dosages; Epididymis; Epididymis - metabolism; Epididymis - pathology; Experiments; Gene expression; Genetic engineering; Germ Cells - cytology; Germ Cells - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Hypotheses; Immunohistochemistry; Infertility; Interdisciplinary aspects; Ligands; Male; Mammals; Medical research; Medicine and Health Sciences; Mice; Notch protein; Proteins - genetics; Proteins - metabolism; Real-Time Polymerase Chain Reaction; Receptors, Notch - antagonists & inhibitors; Receptors, Notch - metabolism; Rodents; Secretase; Signal Transduction - drug effects; Signaling; Spermatogenesis; Spermatogenesis - drug effects; Spermatozoa; Transcription; Transcription Factor HES-1; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113365

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.