A team of CSIR-Centre for Cellular and Molecular Biology (CCMB) scientists has identified eight novel defective genes in men which causes infertility, in their latest study.
“We have identified eight genes (BRDT, CETN1, CATSPERD, GMCL1, SPATA6, TSSK4, TSKS and ZNF318) that were not known earlier, including mutations in them causing impaired sperm production leading to male infertility”, said Mr.Thangaraj, lead investigator of the study and presently director of the DBT-Centre for DNA Fingerprinting and Diagnostics (CDFD) here.
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 this mutation in cellular models and found that it arrests cell division, causing insufficient sperm production.
“This study should be a reminder to the society that half of the infertility cases are due to problems in men. 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 [issues],” remarked Dr Thangaraj.
His group has been researching to understand the genetic causes of male infertility for the past two decades. They have shown earlier that about 38% males with infertility have specific regions missing or abnormalities in their ‘Y’ chromosomes or mutations in their mitochondrial and autosomal genes.
This new multi-institutional study focuses on the cause of infertility in the rest of the cases, which constitutes the majority of infertility-affected men. “We sequenced all the essential regions of all genes (around 30,000) 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 the country,” explained lead author of the study Sudhakar Digumarthi, who was a PhD student at CCMB and presently a scientist at ICMR-National Institute for Research in Reproductive and Child Health in Mumbai.
CCMB director Vinay Kumar Nandicoori pointed out that 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”.
One out of every seven couples are infertile worldwide with male infertility accounting for about 50% of these cases due to 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. But, how these parameters control fertility is not yet understood, said an official release.
The study has been recently published online in the journal Human Molecular Genetics — https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddac216/6682817?guestAccessKey=420cea3d-32f4-4b72-b1c1-59ab558b8f2a.
Other institutions involved in this study are 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-Berhampur; Mamata Fertility Hospital, Secunderabad; and DBT-CDFD, Hyderabad.
