Male infertility: Scientists discover candidate gene for impaired spermatogenesis

July 03, 2001

Lausanne, Switzerland: Researchers in the Netherlands believe they have identified a gene that is involved in causing infertility in men.

Dr Judith Gianotten told the European Society of Human Reproduction and Embryology annual meeting in Lausanne today (Wednesday 4 July) that the ZNF214 gene is probably a candidate gene for impaired spermatogenesis (an inability to make enough sperm cells).

Now they are testing the gene in human testicle cells and mice to discover exactly what role the gene plays in the production (or not) of sperm cells. An understanding of how it works may help researchers in the future to design ways of targeting the gene and developing treatments to men affected by this form of infertility.

Dr Gianotten, a researcher from the Center for Reproductive Medicine at the Amsterdam Academic Medical Center, told the conference that the ZNF214 gene mainly expresses itself in the testis and is located on chromosome 11p15. This part of the chromosome is linked to the Beckwith Wiedemann Syndrome (BWS) - a complex overgrowth disorder, which often involves boys being born with undescended testicles (cryptorchidism) who suffer from infertility as adults1. She said: "For these reasons we hypothesized that ZNF214 could be involved in male subfertility and we decided to test whether this was the case.

"First we investigated whether this gene was associated with impaired spermatogenesis. We found a significantly different distribution of DNA variations in this gene2 in patients with low fertility compared with the control group, which indicated that the gene was indeed associated. So we screened the gene for mutations in men suffering from infertility due to impaired spermatogenesis."

The researchers took DNA from 77 men with very low sperm counts and compared it with DNA from a control group of 65 men with normal sperm counts. In three patients from the infertile group, three new mutations of the ZNF214 gene were found. These mutations were not found amongst the control group.

For two of the patients in whom a mutation was found DNA from their parents was available, and this showed that in both cases the mutation had been inherited from their mothers. All three patients appeared to be normal in every other respect, and none had any symptom of BWS. One of them had a medical history of cryptorchidism.

Dr Gianotten said: "These results suggest that the ZNF214 gene is involved in impaired spermatogenesis, either on its own, or because it causes cryptorchidism which in turn leads to impaired spermatogenesis. In this study only one of the patients in which a mutation was found reported a history of cryptorchidism. This might indicate the involvement of ZNF214 in impaired spermatogenesis on its own. However, it is also possible that ZNF214 is a disease-causing gene for cryptorchidism.

"The fact that the mutation in the gene appears to be inherited from the mother explains how subfertility due to impaired spermatogenesis can be passed on to the next generation. If it was inherited from the father then the mutation would become extinct in the population."

Dr Gianotten said more research was needed to confirm the findings. "At the moment we are preparing studies to see how the gene is expressed in different cell types of human testicles, and we are looking for the identical gene in mice to test the function of the gene and its mutation."
-end-
Abstract no: O-210

Notes

1 The Beckwith-Wiedemann Syndrome (BWS) is a congenital disorder which was described by H.R. Wiedemann in 1963 and J.B. Beckwith in 1969. It is characterised by a variety of symptoms, which include enlarged tongues (macroglossia), abdominal wall defects and gigantisms. Children suffering from BWS have an increased risk of developing childhood tumours in their early years, and cryptorchidism is a symptom in the majority of patients; BWS men have a reduced number of children.

2 In other words, the researchers found significant differences in allele frequencies in patients compared with the controls.

Further information:
Margaret Willson, information officer
Tel: 44-1536-772181
Mobile: 07973-853347
Emma Mason, information officer
Tel: 44-0-1376-563090 Mobile: 07711-296986 Email: m.willson@mwcommunications.org.uk Email: wordmason@aol.com.

Press Office: (Sunday 1 July -Wednesday 4 July)
Margaret Willson, Emma Mason, Janet Blümli
Tel: 41-21-643-33-33 or 41-21-643-33-32 or 41-21-643-33-23
Fax: 41-21-643-33-28.

European Society of Human Reproduction and Embryology

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.