Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells

被引:88
作者
Vernet, Nadege
Dennefeld, Christine
Guillou, Florian
Chambon, Pierre
Ghyselinck, Norbert B.
Mark, Manuel
机构
[1] INSERM, U596, IGBMC, F-67404 Illkirch Graffenstaden, France
[2] CNRS, UMR7104, Illkirch Graffenstaden, France
[3] Fac Med Strasbourg, Strasbourg, France
[4] Univ Tours, INRA, Nouzilly, France
关键词
biological rhythms; germ cells; heterodimers; nuclear receptors; spermatogenesis;
D O I
10.1038/sj.emboj.7601447
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sertoli cells (SC) are instrumental to stem spermatogonia differentiation, a process that critically depends on retinoic acid (RA). We show here that selective ablation of RA receptor alpha (RARalpha) gene in mouse SC, singly (Rara(Ser-/-) mutation) or in combination with RARbeta and RARgamma genes (Rara/b/g(Ser-/-) mutation), abolishes cyclical gene expression in these cells. It additionally induces testis degeneration and delays spermatogonial expression of Stra8, two hallmarks of RA deficiency. As identical defects are generated upon inactivation of RARalpha in the whole organism, our data demonstrate that all the functions exerted by RARalpha in male reproduction are Sertoli cell-autonomous. They further indicate that RARalpha is a master regulator of the cyclical activity of SC and controls paracrine pathways required for spermatogonia differentiation and germ cell survival. Most importantly, we show that the ablation of all RXR (alpha, beta and gamma isotypes) in SC does not recapitulate the phenotype generated upon ablation of all three RARs, thereby providing the first evidence that RARs exert functions in vivo independently of RXRs.
引用
收藏
页码:5816 / 5825
页数:10
相关论文
共 54 条
[1]   Retinoic acid receptor alpha gene expression in the rat testis: Potential role during the prophase of meiosis and in the transition from round to elongating spermatids [J].
Akmal, KM ;
Dufour, JM ;
Kim, KH .
BIOLOGY OF REPRODUCTION, 1997, 56 (02) :549-556
[2]   Heat shock-initiated apoptosis is accelerated and removal of damaged cells is delayed in the testis of clusterin/Apoj knock-out mice [J].
Bailey, RW ;
Aronow, B ;
Harmony, JAK ;
Griswold, MD .
BIOLOGY OF REPRODUCTION, 2002, 66 (04) :1042-1053
[3]   SPERMATOGENIC CELLS OF PREPUBERAL MOUSE - ISOLATION AND MORPHOLOGICAL CHARACTERIZATION [J].
BELLVE, AR ;
CAVICCHIA, JC ;
MILLETTE, CF ;
OBRIEN, DA ;
BHATNAGAR, YM ;
DYM, M .
JOURNAL OF CELL BIOLOGY, 1977, 74 (01) :68-85
[4]   Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter [J].
Benkoussa, M ;
Brand, C ;
Delmotte, MH ;
Formstecher, P ;
Lefebvre, P .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (13) :4522-4534
[5]   Sertoli cell signaling by Desert hedgehog regulates the male germline [J].
Bitgood, MJ ;
Shen, LY ;
McMahon, AP .
CURRENT BIOLOGY, 1996, 6 (03) :298-304
[6]   Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane protein [J].
Bouillet, P ;
Sapin, V ;
Chazaud, C ;
Messaddeq, N ;
Decimo, D ;
Dolle, P ;
Chambon, P .
MECHANISMS OF DEVELOPMENT, 1997, 63 (02) :173-186
[7]   Retinoid signaling determines germ cell fate in mice [J].
Bowles, J ;
Knight, D ;
Smith, C ;
Wilhelm, D ;
Richman, J ;
Mamiya, S ;
Yashiro, K ;
Chawengsaksophak, K ;
Wilson, MJ ;
Rossant, J ;
Hamada, H ;
Koopman, P .
SCIENCE, 2006, 312 (5773) :596-600
[8]   Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes [J].
Calleja, Cecile ;
Messaddeq, Nadia ;
Chapellier, Benoit ;
Yang, Haiyuan ;
Krezel, Wojciech ;
Li, Mei ;
Metzger, Daniel ;
Mascrez, Benedicte ;
Ohta, Kiminori ;
Kagechika, Hiroyuki ;
Endo, Yasuyuki ;
Mark, Manuel ;
Ghyselinck, Norbert B. ;
Chambon, Pierre .
GENES & DEVELOPMENT, 2006, 20 (11) :1525-1538
[9]   The nuclear receptor superfamily:: A personal retrospect on the first two decades [J].
Chambon, P .
MOLECULAR ENDOCRINOLOGY, 2005, 19 (06) :1418-1428
[10]   A decade of molecular biology of retinoic acid receptors [J].
Chambon, P .
FASEB JOURNAL, 1996, 10 (09) :940-954