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Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm
Teng Zi1, YaNan Liu2, YuSheng Zhang2
1Shandong Stem Cell Engineering Technology Research Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Abstract:
Doxorubicin (DOX) is an effective chemotherapy drug, but its clinical use has adverse effects on male reproduction. However, there are few studies about the specific biological processes related to male reproduction or strategies for improving fertility protection. In this paper, we examined the effects of DOX on spermatogenesis and sperm function, and tested the possible protective role of melatonin (MLT) against DOX's reproductive toxicity. DOX-treated mice showed signs of significantly impaired spermatogenesis, including vacuolated epithelial cells, decreased testis weights, and lowered sperm counts and motility. DOX also reduced germ cell proliferation (PCNA) and meiosis-related proteins (SYCP3), but this effect could be partially improved with MLT administration. HSPA2 expression was maintained, which indicated that although MLT did not improve sperm motility, it did have a significant protective effect on elongated sperm. IVF results showed that MLT could partially promote two-cell and blastocyte development that was restricted by DOX. MLT reversed DOX-driven changes in the testes, including the antioxidant indices of SOD1, CAT and PRDX6, and the apoptotic indices of BAX and Caspase3. These results suggest that MLT effectively prevents DOX-induced early reproductive toxicity, and increase our understanding of the molecular mechanisms underlying DOX's effects on male reproduction and the protective mechanism of MLT.
Insights
Melatonin (MLT) protects male fertility against chemotherapy drug Doxorubicin (DOX) toxicity by improving spermatogenesis and sperm function. MLT also reversed DOX-induced oxidative stress and apoptosis in testes.
Area of Science:
- Reproductive Biology
- Toxicology
- Pharmacology
Background:
- Doxorubicin (DOX) is a potent chemotherapy agent with known male reproductive toxicity.
- Limited understanding exists regarding the specific biological pathways affected and protective strategies against DOX-induced male infertility.
Purpose of the Study:
- To investigate the effects of DOX on male reproductive parameters.
- To evaluate the protective potential of melatonin (MLT) against DOX-induced reproductive toxicity.
Main Methods:
- DOX-induced toxicity model in mice.
- Assessment of testicular histology, sperm parameters (count, motility), germ cell proliferation (PCNA), meiosis markers (SYCP3), and HSPA2 expression.
- In vitro fertilization (IVF) assays.
- Measurement of antioxidant (SOD1, CAT, PRDX6) and apoptotic (BAX, Caspase3) markers in testes.
Main Results:
- DOX significantly impaired spermatogenesis, reduced sperm count and motility, and affected germ cell proliferation and meiosis.
- MLT partially ameliorated DOX-induced damage to spermatogenesis and protected elongated sperm.
- MLT improved DOX-compromised two-cell and blastocyst development in IVF.
- MLT reversed DOX-induced oxidative stress and apoptosis in testicular tissues.
Conclusions:
- Melatonin effectively mitigates early-stage Doxorubicin-induced male reproductive toxicity.
- This study elucidates molecular mechanisms of DOX's reproductive effects and MLT's protective actions, offering potential fertility preservation strategies.
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