Abstract
Busulfan and cyclophosphamide (B/C)-treated mice exhibited a marked increase in apoptosis and a concomitant decrease in the ovarian weight. Histological and RT-PCR analysis indicate that the period of germ cell depletion in the B/C-treated ovaries coincides with decreased expression of genes Figla, Lhx8, Nobox, c-kit, and Sox3. However, depletion of the ovarian germ cells is mediated by autophagy-independent pathways that involve Fas/FasL-, TNF-, and/or p53-signalings. Treatment with B/C resulted in the cease of the reproductive function to produce their offspring during the 15(th) week post-treatment period in female mice. Furthermore, injection of the 3 × 10(6) GFP positive primordial follicles into the ovaries of the B/C treated mouse did not show apparent colonization of the transplanted follicles within the recipient ovaries. The present results suggest that B/C treatment is closely associated with an increased risk of premature ovarian failure.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / administration & dosage
-
Antineoplastic Agents / adverse effects*
-
Apoptosis / drug effects
-
Apoptosis / genetics
-
Biomarkers
-
Busulfan / administration & dosage
-
Busulfan / adverse effects
-
Cyclophosphamide / administration & dosage
-
Cyclophosphamide / adverse effects
-
Fas Ligand Protein / genetics
-
Fas Ligand Protein / metabolism
-
Female
-
Gene Expression Regulation
-
Male
-
Mice
-
Oocytes / drug effects
-
Oocytes / metabolism
-
Ovarian Follicle / metabolism
-
Ovarian Follicle / transplantation*
-
Ovary / drug effects*
-
Ovary / pathology
-
Ovary / surgery*
-
Ovum / drug effects
-
Proto-Oncogene Proteins c-kit / genetics
-
Proto-Oncogene Proteins c-kit / metabolism
-
Reproduction / drug effects
-
Signal Transduction
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / metabolism
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / metabolism
-
fas Receptor / genetics
-
fas Receptor / metabolism
Substances
-
Antineoplastic Agents
-
Biomarkers
-
Fas Ligand Protein
-
Tumor Necrosis Factor-alpha
-
Tumor Suppressor Protein p53
-
fas Receptor
-
Cyclophosphamide
-
Proto-Oncogene Proteins c-kit
-
Busulfan