title: Changes in the expression profile of the meiosis-involved mismatch repair genes in impaired human spermatogenesis.
abstract: DNA mismatch repair (MMR) genes have been described to participate in crossover events during meiotic recombination, which is, in turn, a key step of spermatogenesis. This evidence suggests that MMR family gene expression may be altered in infertile men with defective sperm production. In order to determine the expression profile of MMR genes in impaired human spermatogenesis, we performed transcript levels analysis of MMR genes (MLH1, MLH3, PMS2, MSH4, and MSH5), and other meiosis-involved genes (ATR, HSPA2, and SYCP3) as controls, by real-time reverse transcription-polymerase chain reaction in testis from 13 patients with spermatogenic failure, 5 patients with primary germ cell tumors, and 10 controls with conserved spermatogenesis. Correlation of the expression values with the histological findings was also performed. The MMR gene expression values, with the exception of PMS2, are significantly decreased in men with spermatogenic failure. The pattern of MMR reduction correlates with the severity of damage, being maximum in maturation arrest. Specifically, expression of the testicular MSH4 gene could be useful as a surrogate marker for the presence of intratesticular elongated spermatid in patients with nonobstructive azoospermia, contributing to predict the viability of assisted reproduction. Interestingly, a reduction in the MSH4 and MSH5 transcript concentration per spermatocyte was also observed. The decreased expression level of other meiosis-specific genes, such as HSPA2 and SYCP3, suggests that the spermatocyte capacity to express meiosis-related genes is markedly reduced in spermatogenic failure, contributing to meiosis impairment and spermatogenic blockade.
authors.affiliation: Medical and Molecular Genetics Center-Fundació IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Terribas
authors.forename: Sandra
authors.initials: S
authors.lastname: Bonache
authors.forename: Marta
authors.initials: M
authors.lastname: García-Arévalo
authors.forename: Josvany
authors.initials: J
authors.lastname: Sánchez
authors.forename: Eladio
authors.initials: E
authors.lastname: Franco
authors.forename: Lluís
authors.initials: L
authors.lastname: Bassas
authors.forename: Sara
authors.initials: S
authors.lastname: Larriba
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D017398:Alternative Splicing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008540:Meiosis; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; C403623:MLH3 protein, human; C409221:MSH4 protein, human; C118481:MSH5 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D045643:DNA Repair Enzymes