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Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity
Shun-Jen Tan1, Li-Jen Lee2, Chii-Ruey Tzeng3
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No.250 Wusing St., Sinyi District, Taipei 110, Taiwan; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, No.235, Sec.2, Chenggong Rd., Neihu District, Taipei 114, Taiwan.
Abstract:
Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.
Insights
Sphingosine-1-phosphate (S1P) protects ovarian primordial follicles from chemotherapy damage. This targeted therapy may help preserve fertility in cancer patients undergoing chemotherapy.
Area of Science:
- Reproductive biology
- Oncology
- Pharmacology
Background:
- Chemotherapy can cause reproductive system damage by increasing apoptosis (programmed cell death).
- Targeted anti-apoptotic therapies show potential for preserving fertility in patients undergoing chemotherapy.
Purpose of the Study:
- To investigate the protective effect of sphingosine-1-phosphate (S1P) against chemotherapy-induced ovarian damage (gonadotoxicity).
- To assess S1P's role in preserving ovarian function after busulfan treatment in a mouse model.
Main Methods:
- Female mice were treated with busulfan, a chemotherapeutic agent.
- Mice received pre-treatment with low (0.5 mM) or high (2.0 mM) doses of S1P or a vehicle control.
- Ovarian tissue was analyzed histologically and biochemically four weeks post-treatment.
Main Results:
- S1P pre-treatment significantly reduced Caspase 3 immunoreactivity, an indicator of apoptosis, in ovaries.
- More primordial follicles were preserved in S1P-treated ovaries compared to controls.
- Higher mRNA levels of anti-Müllerian hormone (AMH) were observed in S1P-treated mice, suggesting preserved ovarian function.
Conclusions:
- Sphingosine-1-phosphate (S1P) demonstrates a protective effect on primordial follicles against chemotherapy-induced gonadotoxicity.
- S1P may partially preserve overall ovarian function following chemotherapy treatment.
- Targeted S1P therapy is a potential strategy for fertility preservation in cancer patients.
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