sphingosine-1-phosphate and Primary-Ovarian-Insufficiency

To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis. We found that S1P (10 mm) statistically significantly decreased granulosa cell apoptosis after cyclophosphamide (CTX) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with LY294002, PI3K inhibitor.. Treatment with S1P can inhibit the CTX-induced granulosa cell apoptosis. The S1P protective effect is mediated by activating the PI3K/Akt pathway.

Topics: Antineoplastic Agents, Alkylating; Apoptosis; Cells, Cultured; Cyclophosphamide; Drug Evaluation, Preclinical; Female; Granulosa Cells; Humans; Lysophospholipids; Phosphorylation; Primary Ovarian Insufficiency; Proto-Oncogene Proteins c-akt; Sphingosine

To investigate the effects of sphingosine-1-phosphate (S1P) on cyclophosphamid (CTX) and cisplatin (DDP)-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 murine sarcoma.. Fifty-two female C57BL/6 mice were randomized into normal control group (n=10), tumor-bearing model group (n=14), CTX+DDP group (n=14), and S1P+CTX+DDP group (n=14). Before medication and on day 11 of medication during diestrus stage, the mice were sacrificed to measure the ovarian weight, numbers of primordial follicles and growing follicles, tumor weight, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2).. At day 11 of medication, the levels of serum FSH and E2, but not LH, showed significant differences in CTX+DDP group from those in the other groups (P<0.01). FSH, E2, and LH levels were comparable between S1P+CTX+DDP group and the control group (P>0.05). The number of primodial follicles and weight of ovaries in CTX+DDP group decreased significantly compared to those in the other groups (P<0.01). The number of growing follicles in CTX+DDP group was significantly lower than that in the control and model groups(P<0.01), but similar to that in S1P group (P>0.05). The number of primodial follicles and growing follicles and ovarian weight in S1P+CTX+DDP group were close to those in the control and model groups (P>0.05). In CTX+DDP and S1P+CTX+DDP groups, the tumor weight were significantly lower than that in the other two groups (P<0.01), and the tumor inhibition rates were both higher than 60%.. S1P can ameliorate chemotherapy-induced ovarian damage in mice without affecting the efficacy of chemotherapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Female; Lysophospholipids; Mice; Mice, Inbred C57BL; Primary Ovarian Insufficiency; Sarcoma 180; Sphingosine