Reproduction Abstracts

Introduction: While gonadotoxicity of cyclophosphamide (Cy) has been well demonstrated in mice model, the kinetic and effect at different follicular stages are still not well described. Understanding these phenomena is however essential to further develop pharmacological protective approaches. Here, we studied the effect of Cy at different doses and timing on follicular development as well as the potential gonadoprotective effect of the GnRH analogues (GnRHa) during chemotherapy.

Materials and methods: Cyclophosphamide at different doses was injected i.p. (100, 200 and 500 mg/kg). Mice were sacrified at nine different time points between 1 h and 7 days post-injection. In a second experiment, the mice were daily injected with various doses (2, 20, 200 and 500 μg/kg) of GnRHa s.c. or i.m. for 21 days with or without Cy at day14. The followed parameters were evaluated: fertility, estrous cycles by vaginal smears, ovarian reserve by follicular count, growing follicles ratio and immunohistology (TUNEL, caspase-3, Ki67 and AMH).

Results and discussion: The cyclophosphamide induced-follicular depletion was correlated to the dose with a mean follicular loss of 50% after one 200 mg injection. Chemotherapy affected both quiescent and growing follicles. No apoptosis has been observed on primordial and primary follicles despite the pool was already reduced after 24 h. Mechanisms of action of Cy on this pool should be further investigated. GnRHa had no effect on Cy induced-follicular depletion and did not inhibit the pituitary–gonadal axis in mice as effectively as in human.