title: Involvement of ERK phosphorylation in the prevention of ischemia-induced ovarian follicular depletion by stem cells.
abstract: Ovarian failure is commonly caused by aging, autoimmune disease, menopause and cancer therapy. We used an ischemic model in the ovary to test the hypothesis that stem cells are helpful for ovarian regeneration after injury. Three treatment regimes were employed: sham-operated control, ligation plus PBS, and ligation plus immortalized human bone marrow stromal cells (stem cells) groups. After ligation-induced ischemia, stem cells or PBS were injected into rat ovaries. Then, pregnant mare serum gonadotropin was given intra-peritoneally to initiate folliculogenesis. The animals were then sacrificed. The ovary gland was weighed, and ovarian folliculogenesis, stem cell differentiation and vascular neogenesis were evaluated. In order to study improvement of folliculogenesis after ovarian ischemia, steroidogenic acute regulatory protein (StAR), p44/p42 MAPK (T-ERK1/2), and phospho-p44/ p42 MAPK (P-ERK1/2) expression were specifically evaluated. Results indicated that ovarian size was smaller and that the rate of folliculogenesis was lower in ovarian ischemic-reperfusion animals, but both recovered after stem cell treatment. The stem cells migrated into the ovary and differentiated into theca cells, granulosa cells, corona radiata cells and vascular endothelial cells. In addition, von Willebrand factor (vWF) expression was increased; 17beta-estradiol (E2), progesterone (P4), P-ERK1/2 and StAR protein expression was recovered by stem cells treatment in the ischemic ovaries. The serum LH was significantly increased in ovaries of ischemia-reperfusion animals, but the stem cell treatment restored the effects. These results suggest that stem cells might be helpful for ovarian regeneration after injuries by promoting vascular neogenesis and steroidogenesis through the MAPK pathway.
authors.affiliation: Graduate Institute of Transition and Leisure Education for Individuals with Disabilities, Taipei Physical Education College, Taipei, Taiwan, ROC.
authors.forename: Shiow-Chwen
authors.initials: SC
authors.lastname: Tsai
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Su
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Kau
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D007511:Ischemia / Q000150:complications*; D023421:Models, Animal; D006080:Ovarian Follicle / Q000166:cytology* / Q000378:metabolism*; D010053:Ovary / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D014841:von Willebrand Factor; D011374:Progesterone; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases