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Sphingosine 1-phosphate protects ovaries from chemotherapy-induced damage in vivo
Katharina Hancke1, Oliver Strauch, Christine Kissel
1Department of Obstetrics and Gynecology, University of Freiburg School of Medicine, Freiburg, Germany.
Objective:
To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor, would be able to protect ovarian follicles from chemotherapy-induced cell death in vivo.
Design:
Animal study.
Setting:
Academic medical center.
Animal(S):
Twenty female mice.
Intervention(S):
Twenty mice were randomly assigned into three groups: in group A (n = 8), each mouse received an injection of low concentration of S1P (A1: 0.5 mM), prepared in a vehicle (PET) into the bursa of one ovary and a high concentration (A2: 2.0 mM S1P) to the contralateral ovary. In group B (n = 8), only PET was injected to both ovaries. Afterwards, both groups received 100 mug Dacarbazine (Medac, Hamburg, Germany) IV. The control group C (n = 4) received no chemotherapy. After 2 weeks, the ovaries from group C and from 4 mice from group A and B were evaluated histologically. The remaining mice from group A and B were allowed 3 mating attempts at 4, 8, and 12 weeks after chemotherapy.
Main Outcome Measure(S):
Primordial/primary and pre-/antral follicular density, pregnancy rates.
Results:
Chemotherapy caused a significant reduction in the mean number of primordial follicles of mice treated with only PET or with low concentration of S1P (1.86/field of view [C] vs. 1.17 [B] and 0.98 [A1]; P=.006 and P<.0001, respectively) but not in the ovaries treated with high concentration of S1P (2.05/field of view [A2]; P=.918, not significant). Furthermore, three mice (75%) from group A became pregnant at the first mating attempt, in contrast to group B, in which only one mouse (25%) became pregnant and only after the third mating attempt.
Conclusion(S):
Local application of S1P protects ovarian follicles from chemotherapy-induced cell death, thereby preserving fertility.
Insights
Sphingosine-1-phosphate (S1P) protects ovarian follicles from chemotherapy-induced damage. High concentrations of S1P preserved follicle counts and improved pregnancy rates in mice, suggesting a fertility-sparing effect.
Area of Science:
- Reproductive biology
- Oncology
- Pharmacology
Background:
- Chemotherapy often leads to ovarian damage and infertility.
- Sphingosine-1-phosphate (S1P) is known to inhibit apoptosis.
- Protecting ovarian follicles is crucial for preserving fertility in cancer patients.
Purpose of the Study:
- To evaluate the protective effect of S1P on ovarian follicles against chemotherapy-induced cell death.
- To determine if S1P can preserve fertility following chemotherapy treatment in a mouse model.
Main Methods:
- An in vivo animal study was conducted using 20 female mice.
- Mice received local ovarian injections of varying concentrations of S1P or a vehicle control before chemotherapy administration.
- Ovarian follicular density and pregnancy rates were assessed post-treatment.
Main Results:
- Chemotherapy significantly reduced primordial follicle counts, except in ovaries treated with high-concentration S1P.
- High-concentration S1P treatment resulted in significantly higher primordial follicle counts compared to controls.
- Mice treated with high-concentration S1P showed improved pregnancy rates compared to those receiving only the vehicle.
Conclusions:
- Local application of S1P effectively protects ovarian follicles from chemotherapy-induced apoptosis.
- S1P treatment preserves ovarian function and fertility following chemotherapy.
- This study highlights S1P as a potential therapeutic agent for fertility preservation in cancer patients.
