You are currently viewing We now know the gene that causes male infertility.

We now know the gene that causes male infertility.

Male infertility due to non-obstructive azoospermia poses impervious challenges in delineating the exact cause of absent sperms within the ejaculate. A mutation in the gene PNLDC1 guides the production of defective non-coding RNA molecules that are critical to normal spermatogenesis.

Male infertility accounts for about 50% among the one-third of couples battling fertility issues globally. In a subset of infertile men diagnosed with non-obstructive azoospermia, Liina Nagirnaja and colleagues mapped and identified a mutation in a gene that led to the production of RNA molecules that disrupted the process of sperm formation. The men were unable to produce sperms. The gene is the variant PNLDC1. It is a landmark discovery that will propel us into a more detailed understanding of the process of sperm formation and how to treat male infertility with precision.

In the study, Nagirnaja et al. sequenced the genome of 924 men diagnosed with non-obstructive azoospermia. Non-obstructive azoospermia is when a man’s ejaculate contains no sperms despite having patent ducts within the reproductive organs – because the testicular cells don’t manufacture sperms. The study identified four men who had a mutation in the PNLDC1 gene that is critical to spermatogenesis (formation of sperms). A mutation in the gene leads to the production of specific defective non-coding RNA molecules. These RNA molecules are central to error-free spermatogenesis: without which sperm formation will be aberrant. They confirmed this by knocking out the gene from mice. The absence of sperms within an ejaculate is azoospermia.


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Spermatogenesis is a complex and intricate process that involves several genes that encode multiple proteins and similar molecules. The result is sperms that can transfer a man’s genetic material to his off-springs through successful fertilisation upon an entanglement between the woman’s ovum and the man’s sperm. In up to 50% of cases of infertility, the problem is a malefactor. It ranges from slow swimmers to no swimmers at all in the ejaculate.

Identifying this gene is a landmark discovery.  It will guide a deeper understanding of how sperms form. And will guide clinicians into treating male infertility with utmost precision. It may also be a pivotal point in the advancement of male contraception.

The pivotal study is available in the New England Journal of Medicine. You can read it from here.


Dr A. M. Ssekandi is a medical officer, researcher, content creator, author, and founder of He does private practice with a public touch. He is a certified digital marketer. He has earned certificates in Understanding Clinical Research and Writing in Sciences from the University of Cape Town and Stanford University respectively. He also has a certificate of Good Clinical Practice from

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