Hyderabad CCMB study finds mutations in 8 novel genes are linked to male infertility

The causes range from defects in the male reproductive system, deficiencies in semen quality, and hormonal imbalance. Injuries, infections, chronic illness, lifestyle choices and genetic factors can all lead to infertility in males.

What the study did

Dr. K Thangaraj’s group at the CSIR-CCMB has been researching the genetic causes of male infertility for the last two decades. They have earlier shown that about 38 percent of males with infertility have specific regions missing or abnormalities in their Y chromosomes, or mutations in their mitochondrial and autosomal genes.

Their new multi-institutional study focuses on the cause of infertility in the rest of the cases, which constitute the majority of infertility-affected men.

Dr Sudhakar Digumarthi, lead author of the study and 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.”

8 genes not earlier linked to fertility

Dr Thangaraj, lead investigator for the study and 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.”

The team also identified variations (mutations) in these genes that cause impaired sperm production, leading to male infertility.

The researchers 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 society that half of the 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 could be used as potential diagnostic markers for male infertility, and development of improved management strategies for male infertility.”