DNA Damage and Repair in Human Reproductive Cells

Abstract

The fundamental underlying paradigm of sexual reproduction is the production of male and female gametes of sufficient genetic difference and quality that, following syngamy, they result in embryos with genomic potential to allow for future adaptive change and the ability to respond to selective pressure. The fusion of dissimilar gametes resulting in the formation of a normal and viable embryo is known as anisogamy, and is concomitant with precise structural, physiological, and molecular control of gamete function for species survival. However, along the reproductive life cycle of all organisms, both male and female gametes can be exposed to an array of “stressors” that may adversely affect the composition and biological integrity of their proteins, lipids and nucleic acids, that may consequently compromise their capacity to produce normal embryos. The aim of this review is to highlight gamete genome organization, differences in the chronology of gamete production between the male and female, the inherent DNA protective mechanisms in these reproductive cells, the aetiology of DNA damage in germ cells, and the remarkable DNA repair mechanisms, pre- and post-syngamy, that function to maintain genome integrity.

Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

“…The production of healthy gametes is a complex process which requires a series of physiological activities within the reproductive system [ 122 ]. The production of sex hormones is a primary step in the formation of gametes.…”

Features of DNA Repair in the Early Stages of Mammalian Embryonic Development

“…Higher levels of sperm DNA damage are associated with a failure to reach the blastocysts phase and embryonic loss between the embryonic genome activation (EGA) and the blastocyst stages. [ 40 ]. There is evidence that human sperm has a basic BER pathway containing only OGG1 protein [ 41 ].…”

“…However, it is interesting to note that expression of the OGG1 gene in the oocyte at this stage is low [ 42 ]. Some authors consider the random complementarity of sperm cells and oocytes to be an elaborate mechanism for checking the compatibility of oocytes and fertilizing sperm since both must be involved in the restoration of oxidative damage to DNA [ 40 ]. It is believed that BER is the primary pathway for the restoration of oxidative damage in the zygotic genome.…”

The Impact of Single- and Double-Strand DNA Breaks in Human Spermatozoa on Assisted Reproduction

“…Sperm DNA damage is generally categorized as (i) mitochondrial DNA damage, (ii) telomere attrition, (iii) nuclear DNA fragmentation (SDF), (iv) Y-chromosome microdeletions and (v) epigenetic abnormalities ( Figure 1) [6]. SDF can affect one or both strands of the DNA helix, resulting in single-(SSBs) or double-(DSBs) strand DNA breaks [7]. In this narrative review, the mechanisms leading to SSBs and DSBs are described, as well as their association with reproductive outcomes and the molecular mechanisms involved in their repair.…”

“…In this narrative review, the mechanisms leading to SSBs and DSBs are described, as well as their association with reproductive outcomes and the molecular mechanisms involved in their repair. SDF can affect one or both strands of the DNA helix, resulting in single-(SSBs) or double-(DSBs) strand DNA breaks [7]. In this narrative review, the mechanisms leading to SSBs and DSBs are described, as well as their association with reproductive outcomes and the molecular mechanisms involved in their repair.…”