Microsatellite instability and defects in mismatch repair proteins

A new aetiology for sertoli cell-only syndrome

M. R. Maduro, R. Casella, Edward Kim, N. Lévy, C. Niederberger, L. I. Lipshultz, D. J. Lamb

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell-only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predisposition.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalMolecular Human Reproduction
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Sertoli Cell-Only Syndrome
Microsatellite Instability
DNA Mismatch Repair
Staphylococcal Protein A
Microsatellite Repeats
Proteins
Intracytoplasmic Sperm Injections
Sertoli Cells
DNA
Spermatozoa
Testis
Rodentia
Neoplasms
Software
Fibroblasts
Immunohistochemistry
Biopsy
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Cell Biology

Cite this

Microsatellite instability and defects in mismatch repair proteins : A new aetiology for sertoli cell-only syndrome. / Maduro, M. R.; Casella, R.; Kim, Edward; Lévy, N.; Niederberger, C.; Lipshultz, L. I.; Lamb, D. J.

In: Molecular Human Reproduction, Vol. 9, No. 2, 01.02.2003, p. 61-68.

Research output: Contribution to journalArticle

Maduro, M. R. ; Casella, R. ; Kim, Edward ; Lévy, N. ; Niederberger, C. ; Lipshultz, L. I. ; Lamb, D. J. / Microsatellite instability and defects in mismatch repair proteins : A new aetiology for sertoli cell-only syndrome. In: Molecular Human Reproduction. 2003 ; Vol. 9, No. 2. pp. 61-68.
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