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It is estimated that approximately one out of every seven couples are infertile worldwide and that male infertility accounts for half of these cases. A group of scientists believe they have identified defective genes that cause infertility in men.
The researchers have published a paper on their findings in the Human Molecular Genetics of Oxford Academic science journal. The cases of infertility 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 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 per cent of the men with infertility have missing specific genetic regions, 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.
“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,” said Sudhakar Digumarthi, a scientist at ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai.
Digumarthi is also the lead author for the study.
The investigation had identified eight hitherto unknown genes (BRDT, CETN1, CATSPERD, GMCL1, SPATA6, TSSK4, TSKS, and ZNF318), responsible for male infertility, said Thangaraj. He is the lead investigator of this study and presently director of the DBT-Centre for DNA Fingerprinting and Diagnostics, Hyderabad.
‘We have also identified variations (mutations) in these genes that cause impaired sperm production leading to male infertility,’ said 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 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 Thangaraj.
“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,” Vinay Kumar Nandicoori, director, CCMB.
Other institutions involved in this study were: Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru; Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Germany and 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-Centre for DNA Fingerprinting and Diagnostics, Hyderabad were also a part of the study. (ISW)