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.