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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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Expression of prolactin (PRL) protein.(A) 14d group; (B) 21d group; (C) 28d group; (D) 31d group. Original magnification: 400×.
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pone-0016840-g006: Expression of prolactin (PRL) protein.(A) 14d group; (B) 21d group; (C) 28d group; (D) 31d group. Original magnification: 400×.

Mentions: In this study, we found that human stromal cells underwent decidual-like morphologic changes 28 days after human endometrium transplanted. To further confirm this finding, we measured levels of PRL, one of markers of decidualization. After 14 days of hormone treatment (14d group), PRL was mainly expressed in glandular epithelium, while stromal cells were weakly expressed (Fig. 6A). Compared with the 14d group, the 21d group had a higher PRL expression in the glandular epithelium, with no significant increase in the stromal cells (Fig. 6B). Glandular epithelial and stromal cells showed a strong PRL expression 28 days after treated with hormones (28d group) (Fig. 6C). In the 31d group, expression of PRL was not found in the glandular epithelium, with significantly reduced expression in the stromal cells (Fig. 6D). These immunohistochemistry results are consistent with the morphological results which showed that decidualization occurred in endometrial stromal cells in the 28d group.


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

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

Expression of prolactin (PRL) protein.(A) 14d group; (B) 21d group; (C) 28d group; (D) 31d group. Original magnification: 400×.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016840-g006: Expression of prolactin (PRL) protein.(A) 14d group; (B) 21d group; (C) 28d group; (D) 31d group. Original magnification: 400×.
Mentions: In this study, we found that human stromal cells underwent decidual-like morphologic changes 28 days after human endometrium transplanted. To further confirm this finding, we measured levels of PRL, one of markers of decidualization. After 14 days of hormone treatment (14d group), PRL was mainly expressed in glandular epithelium, while stromal cells were weakly expressed (Fig. 6A). Compared with the 14d group, the 21d group had a higher PRL expression in the glandular epithelium, with no significant increase in the stromal cells (Fig. 6B). Glandular epithelial and stromal cells showed a strong PRL expression 28 days after treated with hormones (28d group) (Fig. 6C). In the 31d group, expression of PRL was not found in the glandular epithelium, with significantly reduced expression in the stromal cells (Fig. 6D). These immunohistochemistry results are consistent with the morphological results which showed that decidualization occurred in endometrial stromal cells in the 28d group.

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