Sperm Chromatin Integrity: Etiologies and Mechanisms of Abnormality, Assays, Clinical Importance, Preventing and Repairing Damage


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Volume 1, Issue 3, October-December , Page 147 to 160
Sunday, November 8, 2009 :Received , Tuesday, December 1, 2009 :Accepted


  • - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran
    - Department of Human Nutrition, Faculty of Nutrition & Food Industry, Shaheed Beheshti University of Medical Sciences , Tehran, Iran

  • - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran
  • Corresponding author Ph.D., Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran, P.O. Box: 19615-1177, Tel: +98 21 22432020, Fax: +98 21 22432021, E-mail: Sadeghi@avicenna.ac.ir
    - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran

Abstract:

The standard semen analysis is the first line and the most popular laboratory test in the diagnosis of male fertility. It evaluates sperm concentration, motility, morphology and their vitality. However, it is well-known that normal results of semen analysis can not exclude men from the causes of couples? infertility. One of the most important parameters of sperm in its fertilizing potential is "Sperm chromatin integrity" that has direct positive correlation with Assisted Reproductive Techniques (ART) outcomes including; fertilization rate, embryo quality, pregnancy and successful delivery rate. It seems that sperm DNA chromatin integrity provides better diagnostic and prognostic approaches than standard semen parameters. For these reasons under-standing the sperm chromatin structure, etiology of sperm chromatin abnor-mality, identification factors that disturbs sperm chromatin integrity and the mechanism of their action can help in recognizing the causes of couples? infertility. Various methods of its evaluation, its importance in male fertility, clinical relevance in the outcomes of ART and application of laboratory and medical protocols to improve this integrity have valuable position in diagnosis and treatment of male infertility. There has recently been interest in the subject and its application in the field of andrology. Therefore, with regard to the above mentioned importance of sperm chromatin integrity, this review article describes details of the useful information pertaining to sperm DNA damage including the origins, assessments, etiologies, clinical aspects, and prevention of it.


 

 


Introduction :
Infertility is a major problem in 15-20% of couples trying to conceive in the reproductive ages (1). Male infertility may contribute in half of all couples who refer to infertility clinics (2).
The standard semen analysis is the first line and the most popular laboratory test in the diagnosis of male fertility. It evaluates sperm concentration, motility, morphology and vital-ity. However, it is well-known that normal results of semen analysis can not exclude men from causes of couples? infertility (3).

Today, it is well known that the quality and integrity of sperm chromatin is very important in the reproductive potential of men. Sperm DNA is known to contribute to half of the genomic material of the embryo. Sperm chro-matin is much more compact in somatic cells, with the aim of protecting the paternal genetic materials against damaging factors during its passage from testis as production site to fallopian tubes as final destination (4).
It is a fact that normal sperm genomic

material is required for a normal fertilization, pregnancy, live birth, and postnatal child well being. Therefore, abnormal sperm chromatin may result in male sub-fertility or even infer-tility, recurrent abortion, increased congenital anomalies and testicular cancer in offsprings (5). Thus, more knowledge on sperm chro-matin damage including: etiology, mechan-ism, detection methods, clinical outcomes and treatment may provide better diagnostic and prognostic capabilities than standard sperm parameters for both in vivo and in vitro fertil-izing ability of human spermatozoa (6).

Etiology of sperm chromatin damage
Many factors are involved in inducing sperm DNA damage, which may result in the male infertility. One of these factors is Leuko-cytospermia (7), which is the increase of leuko-cytes in semen due to genital infection and/or inflammation (8).
Leukocytospermia could result in the pro-duction of inflammatory cytokines followed by the overproduction of Reactive Oxygen Species (ROS) leading to increase in sperm DNA damage (9,10). Cigarette smokes also in-duce leukocytospermia and ROS overproduc-tion (11-13). It seems that leukocytes can gener-ate high levels of ROS in semen, which may overwhelm the antioxidant capacity of semen and resultant Oxidative Stress (OS) could dis-turb sperm functions (14, 15).
Also, some of the sperm preparation and cryopreservation protocols could decrease sperm chromatin integrity (16,17). It has been shown that rapid and ultra rapid freezing (flash-freezing in liquid nitrogen) induce the least damage to sperm during cryopreserva-tion (18). Malignancies such as leukemia, Hodgkin’s disease, and testicular malign-nancies could affect sperm chromatin integ-rity by themselves or following their treat-ment with cytotoxic drugs and/ or radiation therapy (19-22).
Many drugs might also affect the semen quality and increase sperm DNA damage
(23-25). Even some types of herbal remedies may induce sperm DNA damage. For ex-ample high dose administration of Gingko biloba, St. John's wort and Echinacae purpura were associated with increased damage of the reproductive cells (26).
Finally, a growing body of evidences shows that environmental and occupational exposures to chemical agents, heat, and agri-cultural toxins could play a role in sperm DNA damage (10). In a recent study, it has been shown that increased scrotal heat not only reduces the quality of semen parameters, but also compromises sperm chromatin integ-rity (27).

Mechanism of Sperm DNA Damage
While the exact causes of sperm DNA damage have not yet been fully elucidated, several interrelated mechanisms have been suggested (28-30). These mechanisms are cat-egorized as abnormal chromatin packaging, apoptosis and oxidative stress.

Abnormal chromatin packaging
The sperm chromatin is an extremely compact and stable structure which must be organized in a specific manner to achieve this unique condensed state (31). This DNA organ-ization provides mor

 


Discussion :
It has recently been accepted that sperm chromatin integrity is an independent index of sperm quality and has better diagnostic and prognostic capacities in association with routine semen analysis results for both in vivo and in vitro fertility. Although there are nu-merous methods to evaluate sperm chromatin integrity, each procedure needs to be studied more and standardized for routine use in diag-nostic andrology lab. However, all of these methods destroy sperm during the evaluation process. Introducing methods with some ef-fect on whole sperm integrity will improve outcomes of ARTs using spermatozoa with approved chromatin integrity. The results may help the physicians to counsel infertile couples referred for ART in a better manner. In addition, sperm preparation techniques and in vitro culture of spermatozoa in special conditions, may develop its quality in men having high percentage of DFI.

 



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