Ceramide-1-phosphate (C1P): Shielding ovarian fertility from chemotherapy-induced damage in a mice model of premature ovarian failure (POF).

PASCUALI, NATALIA; SCOTTI LEOPOLDINA; OUBIÑA, GONZALO; DI PIETRO, MARIANA; MAY, MARÍA; TESONE, MARTA; ABRAMOVICH DALHIA; PARBORELL FERNANDA

Congreso; LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2017

Cancer-directed therapies cause accelerated loss of ovarian reserve leading to POF. As sphingolipid C1P can regulate angiogenesis and apoptosis, we propose it can modulate ovarian function affected by cyclophosphamide (Cy).8-week-old mice (C57BL/6 x Balb/c F1) were given either an i.p. injection of Cy (75 mg/kg) or saline solution only (control). Control and Cy mice underwent sham surgery (intrabursal injection of saline solution), while Cy+C1P mice received intrabursa 5 µl C1P (1 mM). After 2 weeks, mice were euthanized for ovary and uterus collection for histology, IHC and western blot studies. ANOVA followed by Tukey test were performed when needed.We had previously observed that Cy decreases primordial, primary and preantral follicles, while increasing atretic follicles compared to control mice, while in Cy+C1P mice, ovaries recover control numbers of all follicular types. We have now found evidence that Cy increases protein expression of pro-apoptotic BAX (p