Genomic and genetic variation in E2F transcription factor 1 in men with nonobstructive azoospermia

E2F1 gene dosage changes were identified in 7.3% of nonobstructive azoospermic men but rarely occur in the general population, suggesting a role for E2F1 in male fertility.

Carolina J. Jorgez, Ph.D., Nathan Wilken, B.S., Josephine B. Addai, B.S., Justin Newberg, Ph.D., Hima V. Vangapandu, M.S., Alexander W. Pastuszak, M.D., Ph.D., Sarmistha Mukherjee, Ph.D., Jill A. Rosenfeld, M.S., Larry I. Lipshultz, M.D., Dolores J. Lamb, Ph.D.

Volume 103, Issue 1, Pages 44-52


To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH).

Prospective study.

Medical school.

One hundred ten men with NOA and 78 fertile controls.


Main Outcome Measure(s):
The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate CNVs; mutation identification by Sanger sequencing; and histological analyses of testicular tissues.

A microduplication at 20q11.22 encompassing E2F transcription factor-1 (E2F1) was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and in an additional 102 men with NOA screened using Taqman CNV assays, for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls.

E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or overexpressing E2f1.

  • Dolores J Lamb, Ph.D.

    Thank you both for these comments- unfortunately at least to date we have no evidence that E2F1 CNVs are predictive of sperm MicroTESE retrieval outcomes. The incidence of E2F1 CNVs are about as common as Y chromosome micro deletions and this knowledge aids in understanding the etiology of the spermatogenic failure. The mouse models of these defects suggest that gains or losses in E2F1 can affect normal function of other organ systems. I think the prognostic information is valuable and there is no doubt that diagnostic tests will be developed in the near future.

  • Can we use this as a measure of likelihood of finding sperm during a MicroTESE? (i.e. if there is higher experssion of E2F1 – less likely to retrieve sperm with procedure, etc).

  • ranjithrama

    It is interesting that the prevalence of E2F1 CNV was ~8% in men with NOA. This is about half the prevalence of Y-chromosome microdeletions in men with NOA and therefore important. Was a particular histologic variant associated with E2F1 CNV? These authors have presented abstracts demonstrating the importance of E2F1 in testicular descent. What was prevalence of E2F1 CNV in men with cryptorchidism and NOA? Should we advocate screening of E2F1 in men with both abnormalities if prevalence is high?

Translate »