A Clinician's Guide to Sperm DNA and Chromatin Damage by Armand Zini & Ashok Agarwal

Author:Armand Zini & Ashok Agarwal
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

17.3 Epidemiological Indications of Environmentally Induced Changes in Sperm DNA

Genetic or epigenetic changes in the sperm genome introduced by environment- and/or lifestyle-related factors may have a serious impact on the reproductive function of an individual. Thus, such alterations may not only lead to impaired male fertility but, once established, may be paternally passed to the subsequent generations [24, 25].

Although there is no direct evidence of sperm DNA alterations induced by environment/lifestyle and then subsequently passed to the offspring, there are some examples which can be considered as indirect evidence of existence of such mechanisms. The Y chromosome has been argued to be particularly vulnerable to DNA damage because it cannot correct double-stranded DNA deletions by homologous recombination [6].

Paternal smoking, reported to introduce sperm DNA damage [26], has been reported to lead to an increased risk of childhood cancer in offspring [27–29] although others could not find the association [30]. Another possible consequence of sperm DNA damage might be microdeletions in the Y chromosome, which will lead to infertility in the male offspring [31].

It has been suggested, although the data seem somewhat contradictory, that increasing paternal age is associated to a higher frequency of aneuploidies, point mutations, sperm DNA breaks, loss of apoptosis, genetic imprinting and other chromosomal abnormalities and has been considered as the major cause of new mutations in human populations [32]. Apart from age, paternal occupation has been linked to certain birth defects or diseases in the offspring which supposedly would act through genetic or epigenetic mechanisms [33]. Epigenetic abnormalities have been associated to imprinting diseases, for which a paternal role has been reported [34], and have been suggested to be increased in babies following conception by assisted reproduction.

A yet unresolved question being of great importance for evaluation of the risk of transmission of sperm DNA changes to the offspring is the ability of the fertilised oocyte to repair such changes. However, animal experiments might indicate that (1) sensitivity of induction of transmissible genetic damage is germ cell-stage dependent, the male postmeiotic cells being the most sensitive, (2) cytogenetic abnormalities at first metaphase after fertilisation are critical intermediates between paternal exposure and abnormal reproductive outcomes, and (3) the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and that directly affects the risk for abnormal reproductive outcomes is regulated by maternal susceptibility factors [35]. The zygote has machinery necessary for the repair of sperm DNA damage, but the mechanism of action is not fully clarified. It is supposed that such repair should, preferably, take place prior to the first mitotic division and any inadequacies in the repair and replication process may have major adverse consequences for the embryo and also for the health of the offspring [19].

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