Lactoferrin is associated with a decrease in oocyte depletion in mice receiving cyclophosphamide.
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.


METHODS
Complementary DNA microarray and the administration of lactoferrin.


METHODS
Experimental animal study.


METHODS
Female imprinting control region mice.


METHODS
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.


METHODS
A list of nine down-regulated and two up-regulated genes with reliable hybridization signals was obtained. Several target molecules were then investigated.


RESULTS
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.


CONCLUSIONS
The present report suggests that lactoferrin helps to rescue the ability to ovulate and partially to prevent oocyte depletion in mouse ovaries.
Horiuchi
Yuka
Y
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Higuchi
Toshihiro
T
Tatsumi
Keiji
K
Takakura
Kenji
K
Fujii
Shingo
S
Konishi
Ikuo
I
D000818:Animals; D015925:Cryopreservation / Q000379:methods; D003520:Cyclophosphamide / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D004622:Embryo, Mammalian / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D006064:Gonadotropins, Equine / Q000633:toxicity; D007781:Lactoferrin / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000473:pathology / Q000502:physiology; D010060:Ovulation / Q000502:physiology; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics
D018076:DNA, Complementary; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D006064:Gonadotropins, Equine; D012333:RNA, Messenger; D003520:Cyclophosphamide; D007781:Lactoferrin