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.
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.
Authors: Mary B Zelinski; Mark K Murphy; Maralee S Lawson; Andrea Jurisicova; K Y Francis Pau; Natalia P Toscano; Darla S Jacob; John K Fanton; Robert F Casper; Stephen D Dertinger; Jonathan L Tilly Journal: Fertil Steril Date: 2011-03-15 Impact factor: 7.329
Authors: Farners Amargant; Sharrón L Manuel; Megan J Larmore; Brian W Johnson; Maralee Lawson; Michele T Pritchard; Mary B Zelinski; Francesca E Duncan Journal: Biol Reprod Date: 2021-05-07 Impact factor: 4.285
Authors: Michael J Bradaric; Animesh Barua; Krishna Penumatsa; Yu Yi; Seby L Edassery; Sameer Sharma; Jacques S Abramowicz; Janice M Bahr; Judith L Luborsky Journal: J Ovarian Res Date: 2011-02-28 Impact factor: 4.234