Six5 is required for spermatogenic cell survival and spermiogenesis

Partha Sarkar, Sharan Paul, Jennifer Han, Sita Reddy

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1421-1431
Number of pages11
JournalHuman Molecular Genetics
Volume13
Issue number14
DOIs
StatePublished - Jul 15 2004
Externally publishedYes

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Leydig Cells
Spermatogenesis
Cell Survival
Follicle Stimulating Hormone
Testosterone
Oligospermia
Myotonic Dystrophy
Inhibins
Male Infertility
Atrophy
Testis
Alleles
Apoptosis
Serum

ASJC Scopus subject areas

  • Genetics

Cite this

Six5 is required for spermatogenic cell survival and spermiogenesis. / Sarkar, Partha; Paul, Sharan; Han, Jennifer; Reddy, Sita.

In: Human Molecular Genetics, Vol. 13, No. 14, 15.07.2004, p. 1421-1431.

Research output: Contribution to journalArticle

Sarkar, Partha ; Paul, Sharan ; Han, Jennifer ; Reddy, Sita. / Six5 is required for spermatogenic cell survival and spermiogenesis. In: Human Molecular Genetics. 2004 ; Vol. 13, No. 14. pp. 1421-1431.
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