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Age-Dependent De Novo Mutations During Spermatogenesis and Their Consequences

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Genetic Damage in Human Spermatozoa

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1166))

Abstract

Spermatogenesis is a highly complex biological process during which germ cells undergo recurrent rounds of DNA replication and cell division that may predispose to random mutational events. Hence, germ cells are vulnerable to the introduction of a range of de novo mutations, in particular chromosomal aberrations, point mutations and small indels. The main mechanisms through which mutations may occur during spermatogenesis are (i) errors in DNA replication, (ii) inefficient repair of non-replicative DNA damage between cell divisions and (iii) exposure to mutagens during lifetime. Any genetic alteration in the spermatozoa, if not repaired/eliminated, can be passed on to the offspring, potentially leading to malformations, chromosomal anomalies and monogenic diseases. Spontaneous de novo mutations tend to arise and accumulate with a higher frequency during testicular aging. In fact, there is an increased incidence of some chromosomal aberrations and a greater risk of congenital disorders, collectively termed paternal age effect (PAE), in children conceived by fathers with advanced age. PAE disorders are related to well-characterized de novo point mutations leading to a selective advantage on the mutant spermatogonial stem cells that cause a progressive enrichment over time of mutant spermatozoa in the testis.

The purpose of this chapter is to provide a summary on the spontaneous genetic alterations that occur during spermatogenesis, focusing on their underlying mechanisms and their consequences in the offspring.

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Authors and Affiliations

  1. Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Francesca Cioppi, Elena Casamonti & Csilla Krausz

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  1. Francesca Cioppi
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  2. Elena Casamonti
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  3. Csilla Krausz
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Correspondence to Csilla Krausz .

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Editors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy

    Elisabetta Baldi

  2. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Monica Muratori

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Cioppi, F., Casamonti, E., Krausz, C. (2019). Age-Dependent De Novo Mutations During Spermatogenesis and Their Consequences. In: Baldi, E., Muratori, M. (eds) Genetic Damage in Human Spermatozoa. Advances in Experimental Medicine and Biology, vol 1166. Springer, Cham. https://doi.org/10.1007/978-3-030-21664-1_2

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