• PMID: 20692336
• Gene Name: NFE2L2
• Condition: Plays a role in preventing oxidative disruption of spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Plays a role in preventing oxidative disruption of spermatogenesis

Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner

Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortés MM, Hoang YD, Ortiz L, Rau BA, Luderer U.

Oxidative stress occurs when generation of reactive oxygen species (ROS) overwhelms antioxidant defenses. Oxidative stress has been associated with male infertility. The transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) regulates basal and inducible transcription of genes encoding enzymes important for protection against ROS. We hypothesized that deletion of the Nrf2 gene causes testicular and epididymal oxidative stress, which disrupts spermatogenesis. Our results show that male Nrf2(-/-) mice have decreased fertility compared to wild-type and heterozygous littermates, due to accumulating seminiferous tubule damage with increasing age. Testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility in 2-month-old Nrf2(-/-) males did not differ from those of wild-type littermates; however, by age 6 months, Nrf2(-/-) males had 44% lower testicular sperm head counts, 65% lower epididymal sperm counts, and 66% lower epididymal sperm motility than wild-type males. Two- to 4-month-old Nrf2(-/-) males had elevated levels of testicular and epididymal lipid peroxidation and testicular germ cell apoptosis, and decreased levels of antioxidants, compared to wild-type males. These results provide evidence that oxidative stress has deleterious effects on the testis and epididymis and demonstrate a critical role for the transcription factor NRF2 in preventing oxidative disruption of spermatogenesis. CI - Copyright © 2010 Elsevier Inc. All rights reserved. FAU - Nakamura, Brooke N AU - Nakamura BN AD - Department of Medicine, University of California at Irvine, Irvine, CA 92617, USA. FAU - Lawson, Gregory AU - Lawson G FAU - Chan, Jefferson Y AU - Chan JY FAU - Banuelos, Jésus AU - Banuelos J FAU - Cortés, Mabel M AU - Cortés MM FAU - Hoang, Yvonne D AU - Hoang YD FAU - Ortiz, Laura AU - Ortiz L FAU - Rau, Bogdan A AU - Rau BA