Genetics. Y chromosome deletion leading to risk of infertility in Indian men: Study

Globally, one out of seven couples is infertile. In about 50 per cent of them, the reason for not having children lies in problems with the male.

The reasons for male infertility are many. Some of them include total absence of sperm, low sperm production and motility, abnormal sperm shape and function, blockages that prevent sperm delivery due to illnesses and injuries, chronic health problems and lifestyle choices.

In recent years, research has shown that genetic factors play a major role in most of the above causes.

In the Indian context, too, while the trend is similar, the unique and high frequencies of Y chromosome deletion tend to raise the risk of infertility in the male. A recent study by the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, which examined genetic reasons for the deletions, found up to 29.4 per cent of a sample exhibiting the problem.

The findings have potential applications in the infertility clinic. The sperm carrying Y chromosome deletion often leads to failure in assisted reproduction; it will therefore be worthwhile to screen infertile men prior to adapting any assisted reproductive methods, says K Thangaraj, who led the CCMB team in the collaborative study.

Other institutes in the study are: Institute of Reproductive Medicine, Kolkata; Institute and Research Centre, Hyderabad; Central Drug Research Institute, Lucknow; Banaras Hindu University, Varanasi.

Comparative study

According to earlier research by Thangaraj’s group, which has been studying the genetic causes of male infertility for the last two decades, large deletion of the Y chromosome, which consists of several genes, is responsible for male infertility in 8.5 per cent of the cases.

The Y chromosome consists of several genes that are responsible for production of sperms, i.e. spermatogenesis. Deletion of such genes is the most common cause of severe diseases of the testes and spermatogenic defects leading to male infertility, they said.

In the study published online in Scientific Reports , the CCMB team studied the micro to macro deletions on the Y chromosome and the molecular mechanisms behind the deletion events.

The research identified that the Azoospermia Factor (AZF) regions consist of three genetic domains in the long arm of the human Y chromosome referred to as AZFa, AZFb and AZFc, and that they are home to genes required for spermatogenesis.

“We screened 973 infertile men along with 587 fertile men with normal sperm count and motility for AZF regions deletions using several AZF-specific DNA markers, adopting various methodologies, and detected a total of 29.4 per cent of infertile Indian men carrying deletions,” said Deepa Selvi Rani, the lead author of the study.

She added: “We observed a few unique combinations of deletion events exclusively in Indian infertile men.” The study highlights that genetic isolation and endogamy, which is widespread in Indian populations, can play major roles in introducing novel causal variations.

Rakesh Mishra, Director, CCMB, said the Indian population is genetically unique; hence the novel causal deletion events of AFZ regions are not surprising. He further said worldwide data without Indian data is incomplete.

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