Peptides Humanin and MOTS-c Protect Male Fertility from Chemo Damage

Prepubertal cyclophosphamide chemotherapy is a vital treatment for various childhood cancers but often leads to severe reproductive damage and subsequent male infertility. This toxicity can manifest as reduced sperm count, impaired testicular function, and hormonal imbalances, significantly impacting the quality of life for survivors. Despite its prevalence, there remains a critical need for effective therapeutic strategies to mitigate chemotherapy-induced reproductive toxicity and preserve fertility.

The study found that cyclophosphamide significantly impaired reproductive parameters, reducing sperm count by 75% and testicular weight by 50% compared to controls (p<0.001). Both Humanin and MOTS-c treatments substantially ameliorated these detrimental effects. Humanin treatment restored sperm count by 80% and testicular weight by 70% compared to the cyclophosphamide-only group, reaching 85% of control levels (p<0.01). MOTS-c similarly improved sperm count by 72% and testicular weight by 65%, showing a 2.5-fold increase in germ cell survival compared to untreated mice (p<0.05). Furthermore, both peptides significantly reduced markers of oxidative stress and apoptosis (programmed cell death) in testicular tissue, with Humanin decreasing caspase-3 activity by 43% and MOTS-c by 38% (p<0.01).