Ceramide-1-phosphate has protective properties against cyclophosphamideinduced ovarian damage in a mice model of premature ovarian failure

PASCUALI N; SCOTTI L; DI PIETRO M; OUBIÑA G, PASCUALI N, DI PIETRO M, SCOTTI L, LA SPINA F, BUFFONE M, HIGUERA J, ABRAMOVICH D AND PARBORELL F.; BAS D; MAY, MARÍA; GOMEZ MUÑOZ A; CUASNICU P; COHEN D; TESONE M; ABRAMOVICH D; PARBORELL F

HUMAN REPRODUCTION

OXFORD UNIV PRESS

Año: 2018

0268-1161

STUDY QUESTION: Is ceramide-1-phosphate (C1P) an ovarian protective agent during alkylating chemotherapy?SUMMARY ANSWER: Local administration of C1P drastically reduces ovarian damage induced by cyclophosphamide (Cy) via protectionof follicular reserve, restoration of hormone levels, inhibition of apoptosis and improvement of stromal vasculature, while protecting fertility,oocyte quality and uterine morphology.WHAT IS KNOWN ALREADY: Cancer-directed therapies cause accelerated loss of ovarian reserve and lead to premature ovarian failure(POF). Previous studies have demonstrated that C1P regulates different cellular processes including cell proliferation, cell migration,angiogenesis and apoptosis. This sphingolipid may be capable of modulating vascular development and apoptosis in ovaries affected bychemotherapy.STUDY DESIGN, SIZE, DURATION: The 6?8-week-old mice were weighed and administered either a single intraperitoneal injection ofCy (75 mg/kg) or an equal volume of saline solution only for control mice. Control and Cy mice underwent sham surgery and received anintrabursal injection of saline solution, while Cy + C1P animal groups received 5 μl C1P, either 0.5 or 1 mM, under the bursa of both ovaries1 h prior to Cy administration.PARTICIPANTS/MATERIALS, SETTING, METHODS: Animals were euthanized by cervical dislocation or cardiac puncture 2 weeksafter surgery for collection of blood orovary and uterus samples, which were cleaned of adhering tissue in culture medium and used for subsequentassays. Ovaries were used for Western blotting or immunohistochemical and/or histological analyses or steroid extraction, as required(n = 5?8 per group). A set of mice (n = 3/group) was destined for oocyte recovery and IVF. Finally, another set (n = 5?6/group) was separatedto study fertility parameters.MAIN RESULTS AND THE ROLE OF CHANCE: The number of primordial (P < 0.01), primary (P < 0.05) and preantral follicles (P