lactoferrin and Primary-Ovarian-Insufficiency

This study investigated the effect of recombinant human lactoferrin (rhLF) on the premature ovarian failure (POF) of rats. After cyclophosphamide treatments, the POF rats were divided into the following groups: normal control group (NC), low-dose group (LD), medium-dose group (MD) and high-dose group (HD) of rhLF. After drug administrations, the ovarian indexes and hormonal levels were detected. After follicle number count, the proliferation and apoptosis were analyzed with the expressions of genes related with oogenesis, reactive oxygen species (ROS) production and apoptosis detected, followed by the calculation of oxidative stress and protein expressions. After 4-hydroperoxy cyclophosphamide (4-HC) treatments, the effect of rhLF on the proliferation, ROS production and gene expressions of primary rat granulosa cells (GCs) cultured in vitro were detected. After mating, the fertilities of POF rats were recorded. The result showed that the rhLF administrations up-regulated the ovarian index with the number of developing follicles increased and the decreases of hormonal levels conferred. The Ki-67 intensities of the MD and HD groups were up-regulated with the Tunnel intensities decreased. The rhLF treatments significantly promoted the expression of oogenesis, antioxidant and anti-apoptosis related genes. The expression of Bax and Caspase 3 were decreased with the expression of Bcl-2 up-regulated after rhLF administrations. The in vitro treatments of rhLF effectively conferred the toxicity of 4-HC on primary rat GCs. The fertility assessment showed the rhLF treatments up-regulated the offspring's' folliculogenesis, which confirmed the ameliorative role of rhLF on the POF damages via the inhibition of ROS production in GCs.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Cyclophosphamide; Female; Humans; Lactoferrin; Primary Ovarian Insufficiency; Rats; Reactive Oxygen Species

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.. Complementary DNA microarray and the administration of lactoferrin.. Experimental animal study.. Female imprinting control region mice.. 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.. A list of nine down-regulated and two up-regulated genes with reliable hybridization signals was obtained. Several target molecules were then investigated.. 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.. The present report suggests that lactoferrin helps to rescue the ability to ovulate and partially to prevent oocyte depletion in mouse ovaries.

Topics: Animals; Cryopreservation; Cyclophosphamide; DNA, Complementary; Embryo, Mammalian; Female; Forkhead Box Protein O3; Forkhead Transcription Factors; Gonadotropins, Equine; Lactoferrin; Mice; Mice, Inbred ICR; Oligonucleotide Array Sequence Analysis; Oocytes; Ovary; Ovulation; Pregnancy; Primary Ovarian Insufficiency; RNA, Messenger