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Unraveling the Molecular Impact of Sperm DNA Damage on Human Reproduction

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Oxidative Stress and Toxicity in Reproductive Biology and Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1358))

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Abstract

Semen analysis is the cornerstone in the investigation of fertility status of male partner. However, more advanced tests have emerged including the analysis of sperm chromatin integrity and DNA damage as markers of semen quality. This is of particular interest, as preserving the genetic information is essential to achieve a successful reproductive event. Moreover, the presence of unrepaired DNA lesions can affect cellular functions, resulting in the onset of pathological conditions associated with male infertility, and the transmission of diseases to the offspring. Hence, in this chapter, we aim to review the main factors leading to sperm DNA damage, along with the different types of damage which can occur. Furthermore, molecular mechanisms involved in DNA repair during spermatogenesis or after fertilization of the oocyte are described, and the laboratory techniques currently used in diagnostics and research, for the analysis of sperm DNA damage are also presented. Finally, the impact of sperm DNA damage on reproductive outcomes such as fertilization and pregnancy rates will be discussed with a focus on animal and human studies, along with the identification of new markers of sperm chromatin integrity.

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Abbreviations

8-OHdG:

8-hydroxyguanosine

APE1:

AP endonuclease1

AZF:

Azoospermia factor

BER:

Base excision repair

DAPI:

4′,6-diamidino-2-phenylindole

DDR:

DNA damage response

DFI:

DNA fragmentation index

DSB:

Double-strand break

dUTP:

Deoxyuridine triphosphate

FEN-1:

Flap endonuclease-1

GG-NER:

Global genome NER

HSPA2:

Heat shock protein

HR:

Homologous recombination

IUI:

Intrauterine insemination

miRNAs:

microRNAs

MMEJ:

Microhomology-mediated end joining pathway

mtDNA:

Mitochondrial DNA

NAHR:

Non-allelic homologous recombination

NHEJ:

Nonhomologous end-joining

NER:

Nucleotide excision repair

NGS:

Next generation sequencing

ORP:

Oxidation-reduction potential

PCNA:

Proliferating cell nuclear antigen

PARP:

Poly (ADP-ribose) polymerase

Q-FISH:

Quantitative fluorescent in situ hybridization

RPL:

Recurrent pregnancy loss

RR:

Relative risk

RPA:

Replication protein-A

RNA pol II:

RNA polymerase II

rNTPs:

Ribose nucleoside triphosphate

ROS:

Reactive oxygen species

SCD:

Sperm chromatin dispersion

SCSA:

Sperm chromatin structure assay

STS-PCR:

Sequence-tagged site polymerase chain reaction

SSB:

Single-strand break

ssDNA:

Single-stranded DNA

TC-NER:

Transcription-coupled NER

TERC:

Telomerase RNA component

TERT:

Telomerase reverse transcriptase

TUNEL:

Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling

XRCC1:

X-Ray cross-complementing protein 1.

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Authors and Affiliations

  1. American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA

    Renata Finelli & Ashok Agarwal

  2. Department of Anatomy, Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    Bruno P. Moreira & Marco G. Alves

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  1. Renata Finelli
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  2. Bruno P. Moreira
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Correspondence to Ashok Agarwal .

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  1. Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland

    Kavindra Kumar Kesari

  2. Department of Life Science and Bioinformatics, Assam University, Silchar, India

    Shubhadeep Roychoudhury

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Finelli, R., Moreira, B.P., Alves, M.G., Agarwal, A. (2022). Unraveling the Molecular Impact of Sperm DNA Damage on Human Reproduction. In: Kesari, K.K., Roychoudhury, S. (eds) Oxidative Stress and Toxicity in Reproductive Biology and Medicine. Advances in Experimental Medicine and Biology, vol 1358. Springer, Cham. https://doi.org/10.1007/978-3-030-89340-8_5

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