Impact Of Free Radicals Oxidative Stress In The Etiology Of Male Infertility

Traditionally infertility had been viewed as a female problem; now male factor is also considered a major contributory factor to infertility The etiological factors in male infertility has been debated and there is incomplete knowledge about it's pathology The male factor is consrdered a major contributory factor to infertility Apart from the conventional causes for male infertility such as Varicocoele. Cryptorchidism, infections, Obstructive Lesions. Cystic Fibrosis, Trauma, and Tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility.

What are ROS ?

ROS (reactive oxygen species) are a variety of metabolic products derived from the metabolism of molecular oxygen at different cellular level Metabolism of molecular oxygen at this cellular level wrll produce free radicals.

Why spermatozoa are prone to ROS attack?

Sperm cell membrane is rich in unsaturated fatty acid needed for creating membrane fluidity for membrane fusion during fertilization.
At this point. membrane fusion followed by dissolution for emcytosis of acrosin (acrosome reaction) occurs. Acrosin causes dissolution of aona pellucida after which sperm head can enter into ooplasm.
This feature of sperm membrane weakness may be harmful to it as it can be taken by leukocyte prematurely. then there is premature exocytosis of acrosin before the sperm can reach zona, resulting in fertilization failure.

Mechanism of Oxidative Stress :

Lipid peroxidation
Lipids are considered to be the most susceptible macromolecules and are present in sperm plasma membrane in the form of polyunsaturated fatty acids (PUFA), ROS attacks PUFA in the cell membrane, leading to a cascade of chemical reactions cafled lipid per omidation.

Effect on motility
Increased ROS levels also have been correlated with decreased sperm motility, which are associated with a reduction in membrane fluidity that is necessary for sperm -oocyte fusion.

DNA damage by OS
Exposing the sperms to artificially produced ROS causes DNA damage in the form of modification of all bases. production of base-free sites, deletions. frame shifts, DNA cross- links. and chromosomal rearrangements. if the damage is extensive, apoptosis and embryo fragmentation can occur. Decreased fertilization rates and poor embryo cleavage and quality have been reported in infertility cases where sperm samples contain a high frequency of damaged DNA.

Different sources of ROS generating system are:
a) Contaminating leukocytes
b) Abnormal spermatozoa
c) Cytoplasmic droplets
d) Variococele
e) Excessive centrifugation of sperms during sperm preparation.

Natural protective mechanism against ROS:

A. Intracellular:
i. On sperm membrane: alphatocopheroi. vitamin- C, tryptophan. taurine.
ii. On mitochondria: Superoaide dismutase (SOD). glutathione. cataiase

B. Extracellular: ln seminal plasma
i. Glutathione peroxidase
ii. Superooride dismutase
iii. Albumin. vitamin-C

In semen sample. ROS generating and ROS scavenging system exist together. There has to be a balance between both. if it is in favor of ROS generating system, the resulting condition is lrnown as OKIDATNE STRESS. Consequences are:-

1. Abnormal sperm morphology and
2. Abnormal sperm function.

So, in summary it can be said that when pre-oxidants are more powerful than anti-midants, adverse impact on sperm function will follow.

So, ROS generating factors has to be treated first and Pics neutrafized for a better outcome of All? techniques. Supplementing antioxidants in oligospermic, oligoasthenospermic males and in males with high leukocyte count or varicocele has been seen to improve the outcome of ART techniques.