Father's genes affect embryonic development more than previously thought

William Fletcher

Progress Educational Trust

28 June 2009

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[BioNews, London]

The genetic material in sperm has far greater influence over the development of a fertilised egg than was previously imagined. A new joint study from the Huntsman Cancer Institute (HCI) and the IVF and andrology lab at the University of Utah, US, has revealed that the father's sperm passes along a previously unrecognised set of instructions that probably tell the developing embryo which specific genes should be turned on and off. The findings, which could lead to new diagnostic tests to help infertile men, were reported in an advance online publication of the journal Nature.

'Our findings show that the father plays an active role in packaging his genome to help ensure a healthy baby,' said Dr. Brad Cairns, co-leader of the study. 'However, they also raise the possibility that a man's aging, health and lifestyle may alter this packaging and negatively affect fertility and embryo development.'

As a fetus develops, certain genes make choices about organ and tissue development by deciding when key processes are turned on, shut off or put on hold at critical stages. 'But when it comes to development, the sperm is at a real disadvantage. The vast majority of their genes are tightly packed in material that is not helpful in giving them full expression,' explained Cairns, referring to the fact that 96 per cent of sperm DNA is found in a dense, impenetrable material known as 'protamine'.

In every other cell than sperm, DNA molecules are wrapped around structures known as 'histones' which allow easy transmission of their genetic information. Sperm DNA starts off this way too, but as the sperm mature most of the histone proteins are eliminated, eventually leaving just four per cent of the DNA packaged in this manner, with the rest packaged in protamine. This apparent hindrance of an evolutionary adaptation can be explained by a sperm's need to be the one and only winner of the race to reach the egg first - a sperm with DNA packed tightly in protamine is a faster swimmer because it has a smaller and more streamlined head. The hypothesis had been that this four per cent of DNA in histones was randomly distributed. The new work by the Utah group found instead that this DNA is located at important genes for embryonic development. 'Those genes are the important decision makers in the embryo,' Cairns said. 'You need to make sure those genes from the father turn on for normal development... and they have to turn on at the right time.'

Cairns says that he has preliminary evidence that the majority of infertile men have problems in gene packaging due to an incorrect ratio of histones to protamine. 'We are hopeful that this work will soon lead to a clinical diagnostic test that will help couples with infertility problems make better informed decisions regarding their prospects for a healthy child. We will also be testing if aspects of a man's lifestyle - such as age, diet or health - affect proper packaging and fertility.'

Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.