CCMB zeroes in on major genetic causes of male infertility

Hyderabad: CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad has been researching to understand the genetic causes of male infertility for the last two decades. As per the study, 38 per cent of males with infertility have specific regions missing or abnormalities in their chromosomes or mutations in their mitochondrial and autosomal genes.

CCMB's new multi-institutional study focuses on the cause of infertility in the rest of the cases, which constitutes the majority of infertility-affected men. The researchers have identified eight novel genes that were defective in these men in India. The study has been recently published online in the journal Human Molecular Genetics.

Dr Sudhakar Digumarthi, the lead author of the study, who was a Ph D student of CCMB and presently a scientist at ICMR-National Institute for Research in Reproductive and Child Health in Mumbai, said, "We first sequenced all the essential regions of all genes (around 30,000 of them) using next generation sequencing in 47 well-characterised infertile men. We then validated the identified genetic changes in about 1,500 infertile men from different parts of India."

Dr Thangaraj, lead investigator of this study and presently Director of the DBT-Centre for DNA Fingerprinting and Diagnostics, Hyderabad said, "We identified a total of eight genes (BRDT, CETN1, CATSPERD, GMCL1, SPATA6, TSSK4, TSKS and ZNF318), that were not known earlier for their role in human male fertility".

He further said that they have identified variations (mutations) in these genes that cause impaired sperm production leading to male infertility. The researchers have characterised a mutation in one of the eight genes, Centrin 1 (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 the society that half of infertility cases are due to problems in men. And many of them are due to genes that come from the parents, often mothers, of these men. 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 can be used as potential diagnostic markers for male infertility and development of improved management strategies for male infertility".