Journal of Carcinogenesis & Mutagenesis

Adverse Clinical Outcomes Including Impaired Fertility: DNA Damage in Human Spermatozoa

Aitken Robertson^* Department of Biochemistry and Molecular Biology, Georgia Health Sciences University Cancer Center, Augusta, USA
^*Correspondence: Aitken Robertson, Department of Biochemistry and Molecular Biology, Georgia Health Sciences University Cancer Center, Augusta, USA, Email:

Received: 27-Jan-2023, Manuscript No. JCM-23-20054; Editor assigned: 30-Jan-2023, Pre QC No. JCM-23-20054(PQ); Reviewed: 14-Feb-2023, QC No. JCM-23-20054; Revised: 21-Feb-2023, Manuscript No. JCM-23-20054(R); Published: 03-Mar-2023, DOI: 10.35248/2157-2518.23.S36.002

Description

Several unfavorable clinical consequences, such as decreased fertility, a rise in miscarriage rates, and an increased risk of disease in the progeny, have been associated with DNA damage in the male germ line. The following scenarios could theoretically account for the origins of this DNA damage: (i) postmeiotically initiated abortive apoptosis when the capacity to complete this process is declining; (ii) unresolved strand breaks produced during spermatogenesis to relieve the torsional stresses associated with chromatin remodeling; and (iii) oxidative stress. In this paper, we provide a two-step theory for the causes of DNA damage in human spermatozoa that emphasizes the importance of oxidative stress acting on delicate, inadequately protected cells produced as a result of flawed spermatogenesis. We further suggest that these immature cells exhibit various signs of "dysmaturity," such as the retention of too much extracellular cytoplasm, lingering nuclear histones, ineffective zona binding, and altered chaperone content.

These cells may encounter oxidative stress as a result of leukocyte invasion or the entry of spermatozoa into a cascade that resembles apoptosis and is marked by the production of reactive oxygen species by the mitochondria. A decrease in local antioxidant defence, particularly during epididymal growth, may make this oxidative stress worse. Thus, antioxidants should have a significant therapeutic role in the clinical management of male infertility if oxidative stress is a significant contributor to sperm DNA damage. Critically evaluating this possibility currently requires carefully planned studies. Infertility, miscarriages, and birth abnormalities in the offspring are all significantly influenced by DNA damage in the male germ line. The evidence for such a claim mostly comes from the literature on animals, which unmistakably shows that the genetic integrity of the male germ line is crucial in defining the regularity of embryonic development. As a result, the dominant lethal assay, one of the main tools in the toxicologist's arsenal, is based on the core idea that exposing male rats to a particular toxin can hinder the development of any subsequent pregnancies, resulting in high rates of embryonic resorption.

Examples of substances that are effective in the dominant lethal assay are numerous in the toxicological literature, including 1,3- butadiene, diepoxybutane, ethylene thiourea, and acrylamide. Prolonged dominant lethal experiments, which pair treated males with untreated females and check the latter one day before term to check for foetal deformities such as cleft palate or hydrocephaly, have also been advocated. Also, the childrens can be let to grow to adulthood so that tumour susceptibility or behavioral flaws can be researched. With the help of this method, the genotoxic effects of continuous exposure to cyclophosphamide and, in the case of mice, 1,3-butadiene, on male rodents have once again been demonstrated in terms of congenital abnormalities and dominant fatal mutations in the offspring.

In a more recent study, it was investigated if using mouse spermatozoa with DNA damage after a freeze-thaw cycle in the absence of a cryoprotectant had any effect on the development of pregnancy and/or the health and wellbeing of the offspring. The findings of this significant study showed that there were significant negative impacts on embryo development and behaviour, post-natal growth and longevity, and tumour susceptibility in the offspring. Similar investigations have shown a substantial reduction in the embryo implantation rate when spermatozoa are transferred by Intracytoplasmic Sperm Injection (ICSI) after being exposed to a mixture containing putative endonucleases.