title: Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis.
abstract: Through intercellular signalling, the somatic compartment of the foetal testis is able to program primordial germ cells to undergo spermatogenesis. Fibroblast growth factor 9 and several members of the transforming growth factor β superfamily are involved in this process in the foetal testis, counteracting the induction of meiosis by retinoic acid and activating germinal mitotic arrest. Here, using in vitro and in vivo approaches, we show that prostaglandin D2 (PGD2), which is produced through both L-Pgds and H-Pgds enzymatic activities in the somatic and germ cell compartments of the foetal testis, plays a role in mitotic arrest in male germ cells by activating the expression and nuclear localization of the CDK inhibitor p21(Cip1) and by repressing pluripotency markers. We show that PGD2 acts through its Dp2 receptor, at least in part through direct effects in germ cells, and contributes to the proper differentiation of male germ cells through the upregulation of the master gene Nanos2. Our data identify PGD2 signalling as an early pathway that acts in both paracrine and autocrine manners, and contributes to the differentiation of germ cells in the foetal testis.
authors.affiliation: Genetic and Development department, Institute of Human Genetics, CNRS UPR1142, Montpellier 34094, Cedex 05, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Moniot
authors.affiliation: Genetic and Development department, Institute of Human Genetics, CNRS UPR1142, Montpellier 34094, Cedex 05, France.
authors.forename: Safdar
authors.initials: S
authors.lastname: Ujjan
authors.affiliation: Genetic and Development department, Institute of Human Genetics, CNRS UPR1142, Montpellier 34094, Cedex 05, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Champagne
authors.affiliation: Department of Advanced Technology and Development, BML, Matoba, Kawagoe, Saitama 350-1101, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.affiliation: Department of Advanced Technology and Development, BML, Matoba, Kawagoe, Saitama 350-1101, Japan.
authors.forename: Kinya
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Plateforme MGX, Functional Genomic Institute, CNRS UMR 5203 - INSERM U 661, Montpellier 34094, Cedex 05, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Dubois
authors.affiliation: Plateforme MGX, Functional Genomic Institute, CNRS UMR 5203 - INSERM U 661, Montpellier 34094, Cedex 05, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Nidelet
authors.affiliation: Human Gene Sciences Center, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Genetic and Development department, Institute of Human Genetics, CNRS UPR1142, Montpellier 34094, Cedex 05, France francis.poulat@igh.cnrs.fr brigitte.boizet@igh.cnrs.fr.
authors.forename: Francis
authors.initials: F
authors.lastname: Poulat
authors.affiliation: Genetic and Development department, Institute of Human Genetics, CNRS UPR1142, Montpellier 34094, Cedex 05, France francis.poulat@igh.cnrs.fr brigitte.boizet@igh.cnrs.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boizet-Bonhoure
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005333:Fetus / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015230:Prostaglandin D2 / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C477341:Nanos2 protein, mouse; D016601:RNA-Binding Proteins; C490579:Tfdp2 protein, mouse; D014157:Transcription Factors; D015230:Prostaglandin D2
keywords: Differentiation; Embryonic testis; Germ cells; Mitotic arrest; Mouse; Prostaglandin D2