Abstract
A mutation in a single gene, PNLDC1, appears to account for a form of male infertility in which men fail to produce sperm, according to an international study.
This study, published in NEJM, suggests a direct mechanistic effect of faulty P-element–induced wimpy testis–interacting RNA (piRNA) processing on meiosis and spermatogenesis in men, ultimately causing male infertility.
PiRNAs are short, noncoding, and are found almost exclusively in germ cells. The protein PNLDC1 is critical to the processing of piRNAs. It trims their 3′ ends and, when disrupted in mice, causes azoospermia and male infertility.
The researchers sequenced the exomes of 924 men with non-obstructive azoospermia and identified four unrelated men with mutations in the PNLDC1 gene. The length distribution of piRNAs and the number of pachytene piRNAs was significantly altered in these men.
The findings provide insight into how sperm is produced and may one day lead to information helpful for the diagnosis and treatment of non-obstructive azoospermia. Similarly, they may contribute to the development of new methods of male contraception.
