Mystery of idiopathic male infertility Is oxidative stress an actual risk

Capsule:
Sperm ROS formation and DNA damage as well as seminal plasma oxidative stress parameters were investigated in idiopathic infertile men. Intensive oxidative stress may have caused sperm dysfunction.

Authors:
Gülşen Aktan, Ph.D., Semra Doğru-Abbasoğlu, M.D., Canan Küçükgergin, Ph.D., Ateş Kadıoğlu, M.D., Gül Özdemirler-Erata, Ph.D., Necla Koçak-Toker, Ph.D.

Volume 99, Issue 5, Pages 1211-1215, April 2013

Abstract:

Objective:
To study the role of oxidative stress in sperm dysfunction in Turkish idiopathic infertile men.

Design:
Prospective study.

Setting:
Andrology Laboratory of Istanbul Medical Faculty.

Patients:
Semen samples from 28 idiopathic infertile men and 14 fertile men.

Interventions:
Sperm DNA fragmentation and reactive oxygen species (ROS) formation were assayed with the TUNEL test and 2‟,7‟-dichlorodihydrofluorescein respectively. Seminal plasma protein carbonyl groups (PC), nitrotyrosine (NT), malondialdehyde (MDA) and total thiol (SH) levels and ferric reducing antioxidant power (FRAP) were determined.

Main outcome measure:
Sperm DNA fragmentation correlated positively with ROS formation. Both correlated positively with seminal plasma oxidative parameters.

Results:
The number of TUNEL-positive spermatozoa from idiopathic infertile men was higher than that from fertile men, and ROS formation was increased as well in infertile males. A positive correlation was detected between TUNEL-positive cells and ROS content. Seminal plasma MDA, PC and NT levels were elevated in idiopathic infertile males. No difference was observed in the total SH content and FRAP. Seminal plasma MDA levels were correlated positively with both NT and PC levels. Positive correlations were detected between DNA fragmentation and MDA, NT and PC of seminal plasma, and between sperm ROS content and MDA levels.

Conclusion:
The results of this study support the presence of oxidative stress in sperm dysfunction in Turkish idiopathic infertile men.

  • Mike Hsieh

    The relationship between ROS and DNA fragmentation has been shown previously. Despite the confounders of the data that have already been mentioned previously, this article points out the limitation of our current understanding of sperm function and the need for better testing methods. It would be interesting to see if antioxidant therapy or smoking cessation can reverse the observed “sperm dysfunction.”

  • The thing that concerns me about the conclusions is 17 of the 28 idiopathic males were/are active smokers. This can result in elevated oxidative stress, ROS levels, and infertility. So I am unsure we can conclude from this manuscript that the ROS alone is the cause of this cohort’s idiopathic infertility.

    It is well established that increased oxidative stress can result in infertility. The cohort of infertile men have 2/3 that are active smokers, which has also been established to be a cause of free radical formation and oxidative stress.

    We have to be very careful coming to these conclusions when confounding factors are not controlled for.

  • This study raises some very interesting questions but I am concerned about the potential for significant confounding among the cohort of fertile and infertile men. Since it is well documented that obesity can increase systemic oxidative stress, I would be very interested to know the BMI of these two groups of fertile and infertile men. Also, would be helpful to know which groups the smokers were in as this could also increase oxidative stress. While the authors have shown that oxidative stress is increased in the semen and DNA of the infertile group of men it is a significant leap to say that this is the exact cause of their infertility. However, studies such as this are vital to developing tests capable of drilling down on causes of infertility not reflected in a semen analyses. Another possible option would be for the authors to examine the acylation and methylation pathways of these men to determine if their were genetic determinants of their increased oxidative stress as has been previously demonstrated in literature on smoking and bladder cancer risk.

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