title: Modulation of Dhh signaling and altered Sertoli cell function in mice lacking the GPR37-prosaposin receptor.
abstract: The mammalian G-protein-coupled receptor 37 (GPR37) is expressed in brain, in adult testis, and during the early phase of gonad differentiation. Somatic Sertoli cells (SCs) are located within the seminiferous tubules where they support the germinal epithelium. An adequate number of SCs is required for the complete prepubertal differentiation of germ cells and adult fertility. This study shows that Gpr37 and its ligand prosaposin are both postnatally expressed by SCs, whose proliferation and maturation are affected in Gpr37-null mutant mice during postnatal testicular development. Mutant pups show a delayed timing in sperm cell development, with a partial arrest of spermatocytes at the meiotic pachytene (e.g., 1.5-fold increase in Gpr37(-/-) P21 pups) and their increased apoptosis (e.g., 1.8-fold and 3.5-fold increase in Gpr37(-/-) P21 and adult mice, respectively). Mutant adults have reduced testis weight (wild type, 299 ± 5 mg; knockout, 258 ± 16 mg; P < 0.05) and epididymal sperm count and motility (e.g., 1.5-fold and 1.45-fold decrease in Gpr37(-/-) mice, respectively). Lack of Gpr37 results in the reduction in androgen receptor levels during prepubertal testis development, alongside the altered expression of SC maturation markers. It also affects the prepubertal testis expression of desert hedgehog (Dhh) mitogenic cascade components (Dhh, 1.3-fold increase in Gpr37(-/-) P10 and P21 pups; Gli2, 1.4-fold and 1.6-fold increase in Gpr37(-/-) P10 and P21 pups, respectively) including patched homolog 1 (1.3-fold increase in Gpr37(-/-) P10 and P21 pups), which is found localized in prepubertal SCs and is associated with Gpr37 in cultured primary SC samples. These results indicate that Gpr37 is a specific modulator of murine testis Dhh mitogenic signaling and SC proliferation and maturation.
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: La Sala
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marazziti
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Pietro
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Golini
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy.
authors.forename: Rafaele
authors.initials: R
authors.lastname: Matteoni
authors.affiliation: Consiglio Nazionale delle Ricerche, Emma-Infrafrontier-Impc, "A. Buzzati-Traverso" Campus, Istituto di Biologia Cellulare e Neurobiologia, Monterotondo Scalo, Rome, Italy gtocchini@emma.cnr.it.
authors.forename: Glauco P
authors.initials: GP
authors.lastname: Tocchini-Valentini
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049231:Saposins / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000378:metabolism*
chemical_list: C509804:Gpr37 protein, mouse; D053823:Hedgehog Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C483344:Psap protein, mouse; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049231:Saposins
keywords: G-protein-coupled receptor; Ptch1; spermatogenesis; testis