Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity

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Abstract

Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic 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-Müllerian 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.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalReproductive BioMedicine Online
Volume29
Issue number5
DOIs
Publication statusPublished - Nov 1 2014

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Keywords

  • anti-apoptotic therapy
  • anti-Müllerian hormone
  • caspase-3
  • fertility preservation
  • gonadotoxicity
  • sphingosine-1-phosphate

ASJC Scopus subject areas

  • Reproductive Medicine
  • Developmental Biology
  • Medicine(all)

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