CCMB scientists unearth potential diagnostic markers for male infertility

New Delhi: It is estimated that approximately one out of every seven couples is infertile worldwide and that male infertility accounts for half of these cases. The cases range from defects in the male reproductive system to deficiencies in semen quality and hormonal imbalance. Injuries, infections, chronic illness, lifestyle choices, and genetic factors can all lead to infertility in males. Scientists are, however, yet to fully understand the details of how these parameters control fertility.

A group of researchers at the Council of Scientific and Industrial Research’s Hyderabad-based Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, led by Dr. K Thangaraj has been working to elucidate the genetic causes of male infertility for the last two decades. They had earlier shown that about 38% of the men with infertility have missing specific genetic regions or abnormalities in their Y chromosomes or mutations in their mitochondrial and autosomal genes.

The new study which was conducted in collaboration with several other institutions and focused on the cause of infertility in the rest of the cases, has now identified eight defective genes in these men.

Dr Sudhakar Digumarthi, a scientist at ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai, and the lead author of the study said, “We first sequenced all the essential regions of all genes (around 30,000 of them) in 47 well-characterized infertile men, using next generation sequencing. We then validated the identified genetic changes in about 1,500 infertile men.”

Dr Thangaraj, lead investigator of this study and presently Director of the DBT-Centre for DNA Fingerprinting and Diagnostics, Hyderabad, pointed out that the investigation had identified eight hitherto unknown genes (BRDT, CETN1, CATSPERD, GMCL1, SPATA6, TSSK4, TSKS, and ZNF318), responsible for male infertility.

‘We have also identified variations (mutations) in these genes that cause impaired sperm production leading to male infertility,’ said Dr Thangaraj.

The researchers have characterized a mutation in one of the eight genes, CETN1, to understand how the mutation affects sperm production. They demonstrated the impact of CETN1 mutation in cellular models and found that the mutation arrests cell division, causing insufficient sperm production.

“This study should be a reminder to society that half of the infertility cases are due to problems in men. And many of them are due to genes that come from these men’s parents, often mothers. It is wrong to assume a couple cannot bear children because of only the woman’s fertility,” remarked Dr Thangaraj.

Dr Vinay Kumar Nandicoori, Director, CCMB said, “The genetic causes established in this study could be used as potential diagnostic markers for male infertility, and development of improved management strategies for male infertility”.

Other institutions involved in this study were: Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru; Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Germany; All India Institute of Medical Sciences, New Delhi; CSIR-Central Drug Research Institute, Lucknow; Institute of Reproductive Medicine, Kolkata; Indian Institute of Science Education and Research (IISER) Berhampur; Mamata Fertility Hospital, Secunderabad; DBT-Centre for DNA Fingerprinting and Diagnostics, Hyderabad.

The researchers have published a paper on their findings in the Human Molecular Genetics of Oxford Academic science journal.

(India Science Wire)