Vitamin A regulation of BMP4 expression in the male germ line

被引:66
作者
Baleato, RM
Aitken, RJ
Roman, SD
机构
[1] Univ Newcastle, Sch Environm & Life Sci, Reprod Sci Grp, Newcastle, NSW 2308, Australia
[2] Univ Newcastle, Sch Environm & Life Sci, ARC Ctr Excellence & Dev, Newcastle, NSW 2308, Australia
关键词
spermatogenesis; retinoid signaling; BMP4; vitamin A deficiency; testis;
D O I
10.1016/j.ydbio.2005.07.009
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The molecular mechanisms leading to male infertility in vitamin A deficient (VAD) rodents have never been fully elucidated. Here, we report an interaction between BMP4 and retinoid signaling pathways in germ cells that may help clarify the biochemical basis of VAD. Adult germ cells, in particular spermatogonia, expressed BMP4 at both the mRNA and protein levels. BMP4 expression was significantly upregulated in the testes of VAD mice and was down-regulated in freshly isolated germ cells and VAD testes by retinol, but not retinoic acid. The retinoid-responsive gene, RAR beta, was not induced in germ cells following retinoid treatment. Examination of BMP4 promoter usage in spermatogonia and the VAD testis revealed that germ cells utilize the recently characterized BMP4 intron 2 promoter, in addition to the classical 1A and 1B promoters. The observed decrease in BMP4 in response to retinol was mediated by the 1A and intron 2 promoters of the BMP4 gene. Our results reflect a direct requirement for retinoids by germ cells for the resumption of spermatogenesis in VAD animals via mechanisms that involve the suppression of BMP4 expression. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:78 / 90
页数:13
相关论文
共 49 条
[1]   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
[2]   Retinoic acid receptors and retinoid X receptors in the rat testis during fetal and postnatal development: Immunolocalization and implication in the control of the number of gonocytes [J].
Boulogne, B ;
Levacher, C ;
Durand, P ;
Habert, R .
BIOLOGY OF REPRODUCTION, 1999, 61 (06) :1548-1557
[3]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[4]   Role of retinoid signaling in the regulation of spermatogenesis [J].
Chung, SSW ;
Wolgemuth, DJ .
CYTOGENETIC AND GENOME RESEARCH, 2004, 105 (2-4) :189-202
[5]   IDENTIFICATION OF A RETINOIC ACID RESPONSIVE ELEMENT IN THE RETINOIC ACID RECEPTOR-BETA GENE [J].
DETHE, H ;
VIVANCORUIZ, MD ;
TIOLLAIS, P ;
STUNNENBERG, H ;
DEJEAN, A .
NATURE, 1990, 343 (6254) :177-180
[6]   Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: Identification of potential heterodimeric receptors [J].
Dufour, JM ;
Kim, KH .
BIOLOGY OF REPRODUCTION, 1999, 61 (05) :1300-1308
[7]  
FENG JQ, 1995, J BIOL CHEM, V270, P28364, DOI 10.1074/jbc.270.47.28364
[8]   Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse [J].
Fujiwara, T ;
Dunn, NR ;
Hogan, BLM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13739-13744
[9]   Differential expression pattern of retinoid X receptors in adult murine testicular cells implies varying roles for these receptors in spermatogenesis [J].
Gaemers, IC ;
van Pelt, AMM ;
van der Saag, PT ;
Hoogerbrugge, JW ;
Themmen, APN ;
de Rooij, DG .
BIOLOGY OF REPRODUCTION, 1998, 58 (06) :1351-1356
[10]   Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4 [J].
Glozak, MA ;
Rogers, MB .
DEVELOPMENTAL BIOLOGY, 1996, 179 (02) :458-470