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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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Related in: MedlinePlus

Immunohistochemistry of MMP-1, 2, and 9 in transplanted tissues.During the experiment stages, MMP-1, 2 and 9 had different changes in expression level. MMP-1 was expressed in the glandular epithelium and stroma in 14d, 21d and 28d group, and MMP-1 expression was increased in 31d group. MMP-2 was weakly expressed in transplanted tissues in 14d and 21d group, whereas expression in epithelial and stromal cells was significantly increased in 28d and 31d group. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in 14d, 21d and 28d group in expression level. However, MMP-9 expression was increased significantly in 31d group. Original magnification: 200×.
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pone-0016840-g008: Immunohistochemistry of MMP-1, 2, and 9 in transplanted tissues.During the experiment stages, MMP-1, 2 and 9 had different changes in expression level. MMP-1 was expressed in the glandular epithelium and stroma in 14d, 21d and 28d group, and MMP-1 expression was increased in 31d group. MMP-2 was weakly expressed in transplanted tissues in 14d and 21d group, whereas expression in epithelial and stromal cells was significantly increased in 28d and 31d group. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in 14d, 21d and 28d group in expression level. However, MMP-9 expression was increased significantly in 31d group. Original magnification: 200×.

Mentions: Immunohistochemistry results showed that MMP-1 was expressed in the glandular epithelium and stroma 14 days after tissue transplantation. There was no significant change for MMP-1 in the 21d and 28d groups, except in the 31d group in which MMP-1 expression in both glandular epithelial and stromal cells was increased. MMP-2 was weakly expressed in transplanted tissues on day 14 and 21, whereas expression in epithelial and stromal cells was significantly increased on day 28 and day 31. MMP-2 was mainly expressed in the collapsed areas of the xenografts. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in the 14d, 21d and 28d groups at protein level. However, MMP-9 expression was increased significantly in the 31d group (Fig. 8).


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

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

Immunohistochemistry of MMP-1, 2, and 9 in transplanted tissues.During the experiment stages, MMP-1, 2 and 9 had different changes in expression level. MMP-1 was expressed in the glandular epithelium and stroma in 14d, 21d and 28d group, and MMP-1 expression was increased in 31d group. MMP-2 was weakly expressed in transplanted tissues in 14d and 21d group, whereas expression in epithelial and stromal cells was significantly increased in 28d and 31d group. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in 14d, 21d and 28d group in expression level. However, MMP-9 expression was increased significantly in 31d group. Original magnification: 200×.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016840-g008: Immunohistochemistry of MMP-1, 2, and 9 in transplanted tissues.During the experiment stages, MMP-1, 2 and 9 had different changes in expression level. MMP-1 was expressed in the glandular epithelium and stroma in 14d, 21d and 28d group, and MMP-1 expression was increased in 31d group. MMP-2 was weakly expressed in transplanted tissues in 14d and 21d group, whereas expression in epithelial and stromal cells was significantly increased in 28d and 31d group. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in 14d, 21d and 28d group in expression level. However, MMP-9 expression was increased significantly in 31d group. Original magnification: 200×.
Mentions: Immunohistochemistry results showed that MMP-1 was expressed in the glandular epithelium and stroma 14 days after tissue transplantation. There was no significant change for MMP-1 in the 21d and 28d groups, except in the 31d group in which MMP-1 expression in both glandular epithelial and stromal cells was increased. MMP-2 was weakly expressed in transplanted tissues on day 14 and 21, whereas expression in epithelial and stromal cells was significantly increased on day 28 and day 31. MMP-2 was mainly expressed in the collapsed areas of the xenografts. MMP-9 was weakly expressed in glandular epithelium and stromal cells, with no change in the 14d, 21d and 28d groups at protein level. However, MMP-9 expression was increased significantly in the 31d group (Fig. 8).

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