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DOI: 10.1055/s-2006-952554
Sphingosine 1-phosphate protects ovaries from chemotherapy-induced damage in vivo
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.
Interventions: 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 100µg Dacarbazine i.v. The control group C (n=4) received no chemotherapy. After two weeks, the ovaries from group C and from four mice from group A and B were evaluated histologically. The remaining mice from group A and B were allowed three mating attempts at 4, 8 and 12 weeks after chemotherapy.
Main Outcome Measures: 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) 0.98 (A1); p<0.0001 and p<0.0001, respectively], but not in the ovaries treated with high concentration of S1P [2.05 / field of view (A2); p=0.918, n.s.]. 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: Local application of S1P protects ovarian follicles from chemotherapy-induced cell death, thereby preserving fertility.