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.

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Authors

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

Abstract

Objective:

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

Design:

Prospective study.

Setting:

Medical school.

Patient(s):

One hundred ten men with NOA and 78 fertile controls.

Intervention(s):

None.

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.

Result(s):

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.

Conclusion(s):

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02198-0/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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