Genetics and Male Infertility

About Genetics and Male Infertility

- Merlin Nithya Gnanapragasam

Department of Human Genetics, 
School of Medicine, 
 Virginia Commonwealth University, 
U.S.A.  

Infertility is defined as the state in which a couple wanting a child is unable to conceive after 12 months of regular intercourse in the absence of contraceptives. 1 It is a problem faced by couples rather than individuals. ²

Global incidence of infertility is about 13-18%. 1 Male infertility is found to have a role in approximately 50% of infertile couples.³ 

In India, although population growth is a major concern, there are a substantial number of infertile couples. Thus infertility is considered as an important national problem concerning reproductive health.²

Recent advances in assisted reproductive technologies (ART) make it possible for many infertile men with severe male factor infertility to father children. However a significant proportion of infertile males with azoospermia and severe oligozoospermia have a genetic etiology for reproductive failure. ⁴ Thus these technologies raise concerns about passing on genetic abnormalities to the offspring of these men. ⁵ Thus, it is important for the clinicians involved in the treatment of these couples to initiate genetic evaluation and counseling prior to any assisted reproductive procedure

The three most common genetic factors related to male infertility are cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations leading to congenital absence of the vas deferens (CAVD), chromosomal (karyotype) abnormalities and Y-chromosome microdeltions in the azoospermia factor (AZF) locus. ⁴

Infertility can be associated with other far less common genetic conditions. Examples include Kennedy’s disease, Kallman’s syndrome, Prader Willi syndrome, Myotonic dystrophy and Kartagener’s syndrome. ⁶

Gene Therapy Introduction

- Mr.V.G.Prem Kumar

• Gene therapy is a therapeutic procedure which is used to treat Inherited and diseases caused by mutation in DNA and disease caused by infectious diseases. Gene therapy is a very valuable procedure used in cases where there is no conventional treatment available.
• In Gene therapy, Gene transfer is done, in which therapeutic genes are transferred into host cells, in order to modify the genetic information in the cells of the patient.
• Genes have multiple functions to play for proper functioning of an organism, so mutation in a single gene may cause many biological consequences.
• Gene mutation may cause an alteration in enzyme activity causing either an accumulation or deficiency of a substrate, leading to malfunctioning of the normal metabolism. Mutation in a gene coding protein structure may cause cell tissue or organ abnormalities.
• Genetic mutations can cause disorders in every part of the human body including muscles, eyes, liver, bones, kidneys, heart, nerves, skin, brain, stomach, intestines, and blood systems.
• Defect in a gene expressed in one tissue may also cause abnormalities in another organ. The primary goal of human medical genetics research is to develop treatments for different genetic diseases.

Gene Therapy Treatment

- Mr.V.G.Prem Kumar

• Gene therapy is used to treat large number of diseases.
• Research in the field of human gene therapy is directed towards correcting genetic defects of somatic cells i.e., cells that do not contribute to the next generation.
• Human germ line therapy is not tried due to ethical, safety and technical reasons.
• In human somatic cell gene therapy the fully functional and expressible gene is inserted into a target cell, by which that a specific genetic disease can be corrected permanently. 
• The development of a therapeutic agent for human passes through four levels of study and testing:
  
      1. Pre clinical trials that include extensive invitro experiments and
          research on laboratory animals.
  
      2. Phase I trials with a small number (6 to 10) of human 
          subjects.
  
      3. Phase II trials with an increased number of human 
          subjects to examine the effect of the drug or therapy.
  
      4. Phase III trial includes a large human sample and fully 
          comphrensive analysis of the safety and efficacy of   
          the products.