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Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility?

In Europe up to one in four couples experience difficulty conceiving and in half of these cases the problem has been attributed to sub or infertility in the male partner. The development of assisted reproductive technologies (ART) such as in vitro fertilization and intra-cytoplasmic spermatozoa injection has allowed some such couples to achieve a pregnancy. Concerns have been raised over the increasing use of ART not least because of the discovery of elevated levels of DNA damage in sperm from subfertile men. The impact of damaged DNA originating in the male germ line is poorly understood, but is thought to contribute to early pregnancy loss (recurrent miscarriage), placental problems and have a long-term impact on the health of the offspring. DNA repair is essential for meiotic recombination and correction of DNA damage in germ cells and proteins involved in all the major repair pathways are expressed in the testis. In this review, we will consider evidence that the production of sperm containing damaged DNA can be the result of suboptimal DNA repair and/or a mild environmental insult, such as heat stress, and how studies in mice may give us insight into the origins and consequences of DNA damage in human sperm.