Journal
REPRODUCTIVE BIOMEDICINE ONLINE
Volume 29, Issue 5, Pages 612-620Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.rbmo.2014.07.014
Keywords
anti-apoptotic therapy; anti-Mullerian hormone; caspase-3; fertility preservation; gonadotoxicity; sphingosine-1-phosphate
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Funding
- National Science Council Taiwan, R.O.C. [NSC 97-2314-B-016-012-MY2, NSC 99-2314-B-016-013-MY3]
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Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted antiapoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Mullerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function. (C) 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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