Limits...
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.

Show MeSH

Related in: MedlinePlus

Morphological characteristics of xenotransplanted endometrial tissues.(A) Scheme and grouping of the experiment. The ovarectomized mice were allowed to recover for 2 weeks in order to get endogenous hormones free. E2 was administrated in the whole process while P4 was given during day 14 to day 28. The transplanted endometrium tissues were harvested at different time points indicated by downward arrowheads. (B) Photos of transplanted endometrial tissues. a: 28d group; b: 31d group; c: control group without hormone treatment. The red arrowheads indicated transplanted tissues. OVX, removal of both ovaries; E2, estradiol; P4, progesterone.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3040756&req=5

pone-0016840-g001: Morphological characteristics of xenotransplanted endometrial tissues.(A) Scheme and grouping of the experiment. The ovarectomized mice were allowed to recover for 2 weeks in order to get endogenous hormones free. E2 was administrated in the whole process while P4 was given during day 14 to day 28. The transplanted endometrium tissues were harvested at different time points indicated by downward arrowheads. (B) Photos of transplanted endometrial tissues. a: 28d group; b: 31d group; c: control group without hormone treatment. The red arrowheads indicated transplanted tissues. OVX, removal of both ovaries; E2, estradiol; P4, progesterone.

Mentions: The transplanted tissues showed significant differences in general morphology (indicated by red arrows in Fig. 1B) between the different groups. 28 days after hormone treatment (28d group), the tissue fragments with a diameter of 2–3 mm were visible in the subcutaneous tissues (Fig. 1B a). The size of the tissue fragments was increased 1–2 fold compared with that before transplanted, and most tissue fragments were white in color. Blood vessels were clearly visible in the surrounding tissues. Some tissues in the withdrawal group (31d group) were blood red in color (Fig. 1B b), indicating that a good blood supply was established. Compared with those in 28d and 31d group, the tissues transplanted in the control group without hormone support were significantly smaller in size, and wax yellow in color (Fig. 1B c), which suggested that these tissues either stopped growing completely or had their growth inhibited.


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

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

Morphological characteristics of xenotransplanted endometrial tissues.(A) Scheme and grouping of the experiment. The ovarectomized mice were allowed to recover for 2 weeks in order to get endogenous hormones free. E2 was administrated in the whole process while P4 was given during day 14 to day 28. The transplanted endometrium tissues were harvested at different time points indicated by downward arrowheads. (B) Photos of transplanted endometrial tissues. a: 28d group; b: 31d group; c: control group without hormone treatment. The red arrowheads indicated transplanted tissues. OVX, removal of both ovaries; E2, estradiol; P4, progesterone.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016840-g001: Morphological characteristics of xenotransplanted endometrial tissues.(A) Scheme and grouping of the experiment. The ovarectomized mice were allowed to recover for 2 weeks in order to get endogenous hormones free. E2 was administrated in the whole process while P4 was given during day 14 to day 28. The transplanted endometrium tissues were harvested at different time points indicated by downward arrowheads. (B) Photos of transplanted endometrial tissues. a: 28d group; b: 31d group; c: control group without hormone treatment. The red arrowheads indicated transplanted tissues. OVX, removal of both ovaries; E2, estradiol; P4, progesterone.
Mentions: The transplanted tissues showed significant differences in general morphology (indicated by red arrows in Fig. 1B) between the different groups. 28 days after hormone treatment (28d group), the tissue fragments with a diameter of 2–3 mm were visible in the subcutaneous tissues (Fig. 1B a). The size of the tissue fragments was increased 1–2 fold compared with that before transplanted, and most tissue fragments were white in color. Blood vessels were clearly visible in the surrounding tissues. Some tissues in the withdrawal group (31d group) were blood red in color (Fig. 1B b), indicating that a good blood supply was established. Compared with those in 28d and 31d group, the tissues transplanted in the control group without hormone support were significantly smaller in size, and wax yellow in color (Fig. 1B c), which suggested that these tissues either stopped growing completely or had their growth inhibited.

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