A role for epigenetic modifiers in maintaining chromosome integrity during passage through the male gamete in the mouse.

Funded Activity Summary

There is a high level of infertility in the human population, the majority of which remains unexplained. 15% of married couples in the United States are affected by infertility and it is estimated that the male partner is responsible for half of this. Some of this infertility is familial indicating an underlying genetic cause. An increased understanding of the underlying genes involved, should lead to improvements in treatment. The mouse, with its ability to produce large numbers of offspring and its ability to be genetically modified, provides an excellent model system for studying the genetic contribution to reproductive fitness. The studies outlined in this application aim to determine whether a group of genes, previously identified as a result of their effects on epigenetic gene silencing, are also involved in reproductive fitness in the mouse. Our hypothesis is that these genes encode proteins required for normal pairing and segregation of chromosomes during male gametogenesis. While none of the experiments described here involve studies on humans, the genes identified are likely to have human homologues. It will, then, be relatively simple to discover whether infertile men carry mutations in these genes. Assisted reproductive technologies (ART) now accounts for between 1% and 3% of annual births in many western countries and IVF services continue to grow. While these procedures provide an effective treatment for many infertile couples, they promote the transmission of any underlying genetic defects to the next generation. These genetic defects, therefore, need to be identified and understood. Recently it has been reported that the frequency of some rare diseases are, indeed, higher in ART offspring. Furthermore, if our hypothesis is correct and some of the genes involved are critical for chromosome integrity, then mutations in these genes may also increase the risk of cancer later in life.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $390,541.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Developmental Genetics (incl. Sex Determination)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Epigenetics | Inherited diseases | Male infertility | Reproductive health | Spermatogenesis | Transcriptional regulation

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