Sphingosine 1 phosphate suppresses cyclophosphamide induced follicle apoptosis in human fetal ovarian xenografts in nude mice

Capsule:
Antiapoptotic drug sphingosine-1-phosphate suppresses follicular depletion associated with chemotherapeutic agent cyclophosphamide treatment in human fetal ovarian xenografts, potentially providing a new option to prevent infertility associated with cancer treatments.

Authors:
Yuanyuan Meng, M.D., Zhihui Xu, M.D., Fangfang Wu, M.D., Wenming Chen, M.D., Shuangshuang Xie, M.D., Jun Liu, Ph.D., Xuefeng Huang, M.D., Ying Zhou, M.D.

Volume 102, Issue 3, Pages 871-877

Abstract:

Objective:
To investigate the antiapoptosis effect of sphingosine-1-phosphate (S1P) on human fetal ovarian tissue treated by cyclophosphamide (CTX).

Design:
Experimental animal study.

Setting:
University center for reproductive medicine and IVF unit.

Animal(s):
Female immunodeficient BALB/c nude mice, 6 to 8 weeks old.

Intervention(s):
Human fetal ovarian tissue slowly cryopreserved then subcutaneously transplanted in immunodeficient mice.

Main Outcome Measure(s):
Follicle survival assessed qualitatively and quantitatively using H&E staining, and cellular apoptosis of the ovarian grafts evaluated using transmission electron microscopy and DNA nick end labeling in situ (TUNEL assay).

Result(s):
The alkylating agent CTX caused a substantial follicle loss and apoptotic DNA fragmentation in the ovarian grafts in a period of 2 weeks of transplantation. The S1P treatment significantly prevented follicular apoptosis and maintained primordial follicle population in the grafts.

Conclusion(s):
This study shows for the first time that S1P protects primordial follicles in human ovarian grafts from a chemotherapy drug treatment via suppressing follicle apoptosis.

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