Sphingosine 1-phosphate protects ovaries from chemotherapy-induced damage in vivo

Objective: To investigate whether sphingosine-1-phosphate (SIP), 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 and injection of low concentration of S1P (A1: 05 nM), prepared in a vehicle (PET) into the bursa of one ovary and a high concentrate (A2: 2.0 nM S1P) to the contralateral ovary. In group B (n = 8), only PET was injected to both ovaries. Afterwards, both groups received 100 mu g 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 < .001, 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. Conclusion(s): Local application of S1P protects ovarian follicles from chemotherapy-induced cell death, thereby preserving fertility.