Vitamin A regulation of BMP4 expression in the male germ line

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 sp...

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Bibliographic Details
Published in:Developmental biology 2005-10, Vol.286 (1), p.78-90
Main Authors: Baleato, Rosa M., Aitken, R. John, Roman, Shaun D.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
BMP4
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins - genetics
Bone Morphogenetic Proteins - metabolism
Gene Expression Regulation, Developmental - drug effects
Male
Mice
Promoter Regions, Genetic
Receptors, Retinoic Acid - metabolism
Retinoid signaling
RNA, Messenger - genetics
RNA, Messenger - metabolism
Spermatocytes - metabolism
Spermatogenesis
Spermatogenesis - genetics
Spermatogenesis - physiology
Spermatogonia - metabolism
Testis
Vitamin A - pharmacology
Vitamin A deficiency
Vitamin A Deficiency - genetics
Vitamin A Deficiency - metabolism
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Summary: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 up-regulated 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, RARĪ², 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.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2005.07.009