Involvement of ERK Phosphorylation in the Prevention of Ischemia-Induced Ovarian Follicular Depletion by Stem Cells

10.4077/CJP.2010.AMK027

Shiow-Chwen Tsai；Chie-Pein Chen；Tsung-Hsien Su；Mei-Mei Kau；Chien-Chen Lu

stem cell ； ischemia ； ERK ； ovary ； rat

The Chinese Journal of Physiology

53卷3期（2010 / 06 / 01）

167 - 177

英文

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-ERKI/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 ceils 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; 17β-estradiol (E2), progesterone (P4), P-ERK1/2 and StAR protein expression was recovered by stem ceils 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.

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