P-068 Oxidative stress and DNA fragmentation of spermatozoa in patients with cancer
Authors: Calamai C , Ammar O , Rosta V , Krausz C , Giovannelli L , Muratori M 
Published: June 2022

Abstract

Study question
Does cancer increase sperm DNA fragmentation (sDF) level by increasing oxidative stress in human spermatozoa?

Summary answer
Cancer increases both sDF and oxidative stress, but further studies are necessary to understand whether higher levels of ROS are responsible for sperm DNA damage.

What is known already
In recent years, it has been emerging that not only oncological therapies but also cancer itself can induce abnormal spermatogenesis. In addition, several Authors reported that occurrence of malignancy provokes also increases of sperm DNA damage, although such finding was not confirmed by others and the possible mechanisms responsible for such damage are presently unknown

Study design, size, duration
This was a prospective observational study conducted from 2018 to today, conducted in 102 patients affected by cancer and in 66 control subjects.

Participants/materials, setting, methods
We recruited 102 patients affected by cancer and 66 male partners of infertile couples as control subjects, in the Andrology Clinic of University of Florence. Control subjects were normozoospermic with absence of leukocytospermia, semen viscosity, smoking habit and recent antibiotic therapies. In the recruited men, we evaluated standard semen parameters, sperm DNA Fragmentation with SCD (Sperm Chromatin Dispersion) Test and oxidative stress as percentage of viable spermatozoa with MitoSOX™ Red labeling on total viable spermatozoa.

Main results and the role of chance
We found poorer standard semen parameters (sperm motility, concentration and number) in cancer patients (both testicular and hematological ones) with respect to control group, whereas no differences were observed between the two types of cancer. Testicular, but not hematological patients, were younger than control subjects. No difference was seen in the other tested characteristics (sperm morphology, abstinence, semen volume and pH, BMI). Regarding sDF, we found higher median values [IQR] in cancer patients (total: 22.25[17.00-25.95], n = 68; hematological: 23.00[20.13-26.38], n = 28; testicular: 21.13[16.13-25.73], n = 40) vs control subjects (12.50[8.25-14.75], n = 53); p &lt; 0.05, test U di Mann-Whitney. In addition, the amount of sperm oxidative stress was dramatically higher in patients with cancer (total:38.92[24.90-58.87], n = 79; hematological: 38.85[24.98-50.77], n = 34; testicular: 38.92[20.59-63.59], n = 45) vs control subjects (11.50[8.38-17.20], n = 62); p &lt; 0.05, test U di Mann-Whitney. We also studied the occurrence of a correlation between levels of sDF and oxidative stress. We found a sharp correlation when both cancer patients and control subjects were analysed (Spearman coefficient = 0.62, p &lt; 0.001, n = 103), but such correlation was completely lost when only cancer patients were considered (Spearman coefficient = 0.10, p &gt; 0.05, n = 50). This finding suggests that mechanisms different from ROS attack to DNA could explain the increase of sDF levels in cancer patients.

Limitations, reasons for caution
The study did not investigate, because of scarce availability of semen samples from cancer patients, other possible mechanisms (i.e apoptosis, defects in sperm chromatin maturation, failure in DNA system repair) which could cause the observed increase of sperm DNA damage in such patients.

Wider implications of the findings
Cancer patients show high levels of both sDF and oxidative stress. This finding rises concern, as cancer patients cryopreserve semen for using it with Assisted Reproductive Tecnhologies and both parameters represent a threat for natural and assisted reproduction. In addition, emerging evidence suggest that oxidative stress may alter sperm epigenome.

Trial registration number
not applicable