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Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model.

Guo Y, He B, Xu X, Wang J - PLoS ONE (2011)

Bottom Line: Human CD45+ cells showed a peak of increase 28 days post-transplantation.Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts.After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, People's Republic of China.

ABSTRACT
In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

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Human and mouse CD31 expression in xenotransplanted endometrial tissues.(A) hCD31 expression in endometrial tissues after transplantation. There were a large number of human blood vessels in transplanted tissues, while the mouse tissues surrounding transplanted tissues also have hCD31 expression. The image in the right (b, c) is a magnification of the image on the left (a). Original magnification: 400×. (B) mCD31 expression in endometrial tissues after transplantation. (a) and (b) are from serial thin sections. The mCD31+ blood vessels were indicated by red arrowhead in (b, c) which is also indicated by oval-shaped region in (a). (c) is a magnification of (b). Original magnification: 400×.
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pone-0016840-g007: Human and mouse CD31 expression in xenotransplanted endometrial tissues.(A) hCD31 expression in endometrial tissues after transplantation. There were a large number of human blood vessels in transplanted tissues, while the mouse tissues surrounding transplanted tissues also have hCD31 expression. The image in the right (b, c) is a magnification of the image on the left (a). Original magnification: 400×. (B) mCD31 expression in endometrial tissues after transplantation. (a) and (b) are from serial thin sections. The mCD31+ blood vessels were indicated by red arrowhead in (b, c) which is also indicated by oval-shaped region in (a). (c) is a magnification of (b). Original magnification: 400×.

Mentions: General observation showed that transplanted tissues were increased in volume, which indicated that the blood supply must be established between transplanted human tissues and host mouse tissues. In our study, a large number of human CD31+ cells were observed in transplanted tissues, suggesting that transplanted human tissues were rich in human blood vessels (Fig. 7A c). Mouse tissues around the transplanted human tissues also contained a small amount of human CD31+ signals, suggesting the growth of human blood vessels into the near mouse tissues or the infiltration of human endothelial cells (Fig. 7A b). We also found that the transplanted tissues contained mouse CD31+ cells forming duct-like structures (Fig. 7B), which indicated that transplanted tissue also contained mouse blood vessels.


Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model.

Guo Y, He B, Xu X, Wang J - PLoS ONE (2011)

Human and mouse CD31 expression in xenotransplanted endometrial tissues.(A) hCD31 expression in endometrial tissues after transplantation. There were a large number of human blood vessels in transplanted tissues, while the mouse tissues surrounding transplanted tissues also have hCD31 expression. The image in the right (b, c) is a magnification of the image on the left (a). Original magnification: 400×. (B) mCD31 expression in endometrial tissues after transplantation. (a) and (b) are from serial thin sections. The mCD31+ blood vessels were indicated by red arrowhead in (b, c) which is also indicated by oval-shaped region in (a). (c) is a magnification of (b). Original magnification: 400×.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040756&req=5

pone-0016840-g007: Human and mouse CD31 expression in xenotransplanted endometrial tissues.(A) hCD31 expression in endometrial tissues after transplantation. There were a large number of human blood vessels in transplanted tissues, while the mouse tissues surrounding transplanted tissues also have hCD31 expression. The image in the right (b, c) is a magnification of the image on the left (a). Original magnification: 400×. (B) mCD31 expression in endometrial tissues after transplantation. (a) and (b) are from serial thin sections. The mCD31+ blood vessels were indicated by red arrowhead in (b, c) which is also indicated by oval-shaped region in (a). (c) is a magnification of (b). Original magnification: 400×.
Mentions: General observation showed that transplanted tissues were increased in volume, which indicated that the blood supply must be established between transplanted human tissues and host mouse tissues. In our study, a large number of human CD31+ cells were observed in transplanted tissues, suggesting that transplanted human tissues were rich in human blood vessels (Fig. 7A c). Mouse tissues around the transplanted human tissues also contained a small amount of human CD31+ signals, suggesting the growth of human blood vessels into the near mouse tissues or the infiltration of human endothelial cells (Fig. 7A b). We also found that the transplanted tissues contained mouse CD31+ cells forming duct-like structures (Fig. 7B), which indicated that transplanted tissue also contained mouse blood vessels.

Bottom Line: Human CD45+ cells showed a peak of increase 28 days post-transplantation.Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts.After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, People's Republic of China.

ABSTRACT
In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

Show MeSH
Related in: MedlinePlus