Low sperm counts linked to increased risk of genetic disorders

17 May 2005

Genomic imprinting is a process of differential expression of certain genes in the foetus based on whether they are present on the paternal or maternal alleles. Imprinting is mediated by epigenetic modifications, of which the most common is differential methylation of DNA sequences associated with imprinted genes in oocytes and spermatozoa. Major changes in genomic methylation occur following fertilisation, but imprinted alleles are protected from these effects. Imprinting disorders can lead to abnormal foetal development and diseases such as Angelman's and Beckwith-Wiedemann's syndromes. Angelman syndrome results in severe learning difficulties, epilepsy, unsteady gait and an unusually happy disposition. In some cases the syndrome is caused by DNA mutations that disrupt the imprinting process in a region of chromosome 15. Beckwith-Wiedemann syndrome is a condition associated with excessive growth before and after birth; this can cause a range of physical abnormalities, and also confers a greatly increased risk of malignant tumour development. In up to 60% of cases it is thought to result from disruption of imprinting in a region of chromosome 11.

Concern over the risk of imprinting disease in children conceived using assisted reproductive technologies (ARTs) such as in vitro fertilisation has been raised due to an unexpectedly high incidence of these syndromes. This has previously been attributed to the loss of maternal imprinting in the oocyte or embryo caused by ART procedures such as oocyte maturation or embryonic culture. A new study published in the Lancet presents evidence linking genetic imprinting disorders with abnormal spermatogenesis in men with low sperm counts [Marques CJ et al. (2004) Lancet 363, 1700-1702].

The Portugese team analysed spermatozoa from semen samples from 123 men undergoing routine investigations for infertility. Of these, 27 were found to have normal sperm and were used as a control group, whilst the remainder had moderate (46 individuals) or severe (50 individuals) oligozoospermia