OBJECTIVE: To investigate new important molecules involved in the regulation of chemotherapy-induced ovarian damage and, based on those results, to examine the effect of lactoferrin on cyclophosphamide (CPM)-induced ovarian failure. DESIGN: Complementary DNA microarray and the administration of lactoferrin. SETTING: Experimental animal study. ANIMAL(S): Female imprinting control region mice. INTERVENTION(S): Administration of CPM to mice, isolation of ovaries, isolation of RNA, microarray hybridization, and statistical analysis. According to the results of the microarray assay, administration of lactoferrin to CPM-treated mice, isolation of ovaries, isolation of RNA, and evaluation using quantitative polymerase chain reaction and histomorphometric analyses. MAIN OUTCOME MEASURE(S): A list of nine down-regulated and two up-regulated genes with reliable hybridization signals was obtained. Several target molecules were then investigated. RESULT(S): Among the listed genes, we focused on the mouse lactoferrin gene, because of its CPM-induced expression pattern and its multiple novel functions. Oral administration of bovine lactoferrin prevented down-regulation of the ovulation-related, Adamts1 and partial recovery of follicle depletion induced by CPM treatment. CONCLUSION(S): The present report suggests that lactoferrin helps to rescue the ability to ovulate and partially to prevent oocyte depletion in mouse ovaries.
OBJECTIVE: To investigate new important molecules involved in the regulation of chemotherapy-induced ovarian damage and, based on those results, to examine the effect of lactoferrin on cyclophosphamide (CPM)-induced ovarian failure. DESIGN: Complementary DNA microarray and the administration of lactoferrin. SETTING: Experimental animal study. ANIMAL(S): Female imprinting control region mice. INTERVENTION(S): Administration of CPM to mice, isolation of ovaries, isolation of RNA, microarray hybridization, and statistical analysis. According to the results of the microarray assay, administration of lactoferrin to CPM-treated mice, isolation of ovaries, isolation of RNA, and evaluation using quantitative polymerase chain reaction and histomorphometric analyses. MAIN OUTCOME MEASURE(S): A list of nine down-regulated and two up-regulated genes with reliable hybridization signals was obtained. Several target molecules were then investigated. RESULT(S): Among the listed genes, we focused on the mouselactoferrin gene, because of its CPM-induced expression pattern and its multiple novel functions. Oral administration of bovinelactoferrin prevented down-regulation of the ovulation-related, Adamts1 and partial recovery of follicle depletion induced by CPM treatment. CONCLUSION(S): The present report suggests that lactoferrin helps to rescue the ability to ovulate and partially to prevent oocyte depletion in mouseovaries.