Improvement of ovarian response by administration of bioactive sphingolipid Ceramide-1-phosphate (C1P) in aged female mice.

PASCUALI NATALIA; IRUSTA GRISELDA; FERNANDA PARBOREL; SCOTTI LEOPOLDINA; TESONE MARTA; ABRAMOVICH DALHIA; DI PIETRO MARIANA; GOMEZ MUÑOZ ANTONIO

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

For a variety of reasons,many women postpone childbearing over 38 years,and a considerable proportion of aged female become infertile. Ovarianaging is dominated by a progressive loss of primordial follicles and decline inthe quality of oocytes. The activation of ovarian angiogenesis has emerged as anew strategy for the improvement of age-related decline of ovarian response.Since the bioactive sphingolipid C1P is an important proangiogenic andanti-apoptotic factor, our aim was to study whether C1P can improve the ovarianresponse and angiogenesis in aged female mice.Aged female mice (26-31 weeks) received C1P(10µl/ovary; 50µM) under the bursa of one ovary and vehicle on the other ovary,and were sacrificed 48h post-surgery. Young mice (6-9 weeks) were used ascontrol. Ovaries were isolated for histological and immunohistochemical analysis(VW and SMA; endothelial and periendothelial cell markers, respectively),radioimmunoassay (E2 and P4 concentrations) and western blot (pFoxo3a/Foxo3aand AMH; ovarian reserve markers).The % of primary (PF), preantral (PrF) and antralfollicles (AF) in aged mice were lower than in young mice (p<0,05). C1Ptreatment increased the % of PrF and AF in aged mice (p<0,05). The % ofatretic follicles (AtrF) in aged mice was higher than in young mice (p<0,01)and C1P decreased the % of AtrF (p<0,05) in aged mice. C1P increased theconcentration of ovarian E2 and P4 in aged mice (p<0,05). C1P decreasedpFoxo3a/Foxo3a ratio and increased AMH levels in aged mice (p<0,05). Theendothelial and periendothelial cell area increased in ovaries from aged mice treated with C1P (p<0,05).  In conclusion, C1P administration in aged miceincreased the ovarian response, possibly by preserving the ovarian reserve andincreasing the ovarian angiogenesis. These results may have potential clinicalimplications in the treatment of age-related infertility.