Journal Article

<i>Six5</i> is required for spermatogenic cell survival and spermiogenesis

Partha S. Sarkar, Sharan Paul, Jennifer Han and Sita Reddy

in Human Molecular Genetics

Volume 13, issue 14, pages 1421-1431
Published in print July 2004 | ISSN: 0964-6906
Published online May 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddh161
Six5 is required for spermatogenic cell survival and spermiogenesis

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Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia, Leydig cell hyperproliferation and increased follicle stimulating hormone (FSH) levels. DM1 results from a CTG expansion that causes transcriptional silencing of the flanking SIX5 allele. Loss of Six5 results in male sterility and a progressive decrease in testicular mass with age. We demonstrate a strict requirement of Six5 for both spermatogenic cell survival and spermiogenesis. Leydig cell hyperproliferation and increased intra-testicular testosterone levels are observed in the Six5−/−mice. Although increased FSH levels are observed in the Six5+/−and Six5−/−mice, serum testosterone levels and intra-testicular inhibin alpha and inhibin beta B levels are not altered in the Six5 mutant animals when compared with controls. Significantly, steady-state c-Kit levels are reduced in the Six5−/− testis. Thus, decreased c-Kit levels could contribute to the elevated spermatogenic cell apoptosis and Leydig cell hyperproliferation in the Six5−/− mice. The results support the hypothesis that the reduced SIX5 levels contribute to the male reproductive defects in DM1.

Journal Article.  6961 words.  Illustrated.

Subjects: Genetics and Genomics

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