Fertility Impacts of Cancer Treatments on Male Reproductive Health

Male fertility can be profoundly affected by cancer therapies, notably by chemotherapy, radiotherapy and surgical interventions. These treatments commonly damage the testicular germinal epithelium, leading to impaired spermatogenesis, hormonal dysregulation and structural alterations in seminiferous tubules. Chemotherapeutic agents such as bleomycin, etoposide and cisplatin generate oxidative stress and induce apoptosis in developing germ cells, often resulting in reduced sperm counts, poor motility and elevated rates of sperm DNA fragmentation. Radiotherapy can disrupt the hypothalamic–pituitary–gonadal axis and compromise Leydig cell function, while orchiectomy removes germinal tissue entirely. Long-term consequences range from transient oligozoospermia to permanent azoospermia, with risks of chromosomal abnormalities and aneuploidy persisting for months to years after treatment. Fertility preservation strategies—including sperm cryopreservation, testicular tissue banking and the use of cytoprotective agents—have gained traction. An integrated understanding of the mechanisms driving genotoxicity, alongside clinical approaches to mitigate damage, underpins emerging protocols designed to safeguard reproductive potential in male cancer survivors.

Research from Nature Portfolio

Recent studies have explored protective interventions against chemotherapy-induced testicular toxicity. In a rodent model exposed to a bleomycin-etoposide-cisplatin regimen, co-administration of sodium alginate significantly ameliorated testicular damage. Treated animals demonstrated preservation of sperm count and motility, restoration of serum testosterone levels and improved seminiferous tubule histology. Mechanistically, sodium alginate enhanced total antioxidant capacity and reduced lipid peroxidation and nitric oxide accumulation within testicular tissue. At the molecular level, it modulated apoptotic pathways by upregulating anti-apoptotic Bcl-2 and downregulating pro-apoptotic Bax, Caspase-3 and p53, thereby attenuating inflammation and cell death. These findings point to the feasibility of adjunctive antioxidant therapy in reducing chemotherapy-related gonadotoxicity without compromising antineoplastic efficacy.

Fertility Impacts of Cancer Treatments on Male Reproductive Health publication trend

The graph below shows the total number of articles in fertility impacts of cancer treatments on male reproductive health across all publications each year (not limited to Nature Index journals).

Technical terms

Spermatogenesis: The process by which spermatozoa are produced from spermatogonial stem cells within the seminiferous tubules.

Aneuploidy: A condition in which spermatozoa carry an abnormal number of chromosomes, often resulting from mis-segregation during meiosis.

Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defences, leading to cellular and DNA damage.

DNA fragmentation: The occurrence of breaks within sperm nuclear DNA strands, impairing genomic integrity and fertility potential.

Cytoprotective agent: A compound administered alongside chemotherapy to shield non-malignant cells from toxic insult without reducing anticancer activity.

References

1. Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis. Scientific Reports (2024).
2. Effects of Chemotherapy on Aneuploidy Rates in Sperm from Male Patients with Testicular Cancer or Hodgkin’s Lymphoma—A Systematic Review. Journal of Clinical Medicine (2024).
3. Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma. PLOS ONE (2020).