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Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation.

Jensen F, Woudwyk M, Teles A, Woidacki K, Taran F, Costa S, Malfertheiner SF, Zenclussen AC - PLoS ONE (2010)

Bottom Line: Mast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus.Moreover, MC degranulation correlates with angiogenesis during pregnancy.By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation.

View Article: PubMed Central - PubMed

Affiliation: Experimental Obstetrics & Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. federico.jensen@med.ovgu.de

ABSTRACT

Background: Mast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus. Moreover, MC degranulation correlates with angiogenesis during pregnancy. The number of MCs in the uterus has been shown to fluctuate during menstrual cycle in human and estrus cycle in rat and mouse indicating a hormonal influence on their recruitment from the periphery to the uterus. However, the mechanisms behind MC migration to the uterus are still unknown.

Methodology/principal findings: We first utilized migration assays to show that MCs are able to migrate to the uterus and to the fetal-maternal interface upon up-regulation of the expression of chemokine receptors by hormonal changes. By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation.

Conclusion/significance: We propose that estradiol and progesterone modulate the migration of MCs from the periphery to the uterus and their degranulation, which may prepare the uterus for implantation.

Show MeSH
Human MCs actively migrate towards human trophoblast cells as well as to uterine cells treated with hormones.Using a two-chamber trans-well system, the migration of HMC-1 cells to primary first trimester trophoblasts (Fig. 2A) or JEG-3 cells (Fig. 2B) as well as to uterine cell line (AN3-CA) (Fig. 2C) upon hormonal treatment was analyzed at different time points (0, 4, 8, 24, and 48 h) by determining the relative number of HMC-1-CD117+ cells present in the lower part of the system referred to the total number of CD117+ cells in the upper and lower chambers. Spontaneous migration (ca. 5%) was subtracted for all time points. Data are representative of four experiments done in duplicates each. *:p<0.05 and **:p<0.01 as analyzed by ANOVA test followed by Tukey's test.
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pone-0014409-g002: Human MCs actively migrate towards human trophoblast cells as well as to uterine cells treated with hormones.Using a two-chamber trans-well system, the migration of HMC-1 cells to primary first trimester trophoblasts (Fig. 2A) or JEG-3 cells (Fig. 2B) as well as to uterine cell line (AN3-CA) (Fig. 2C) upon hormonal treatment was analyzed at different time points (0, 4, 8, 24, and 48 h) by determining the relative number of HMC-1-CD117+ cells present in the lower part of the system referred to the total number of CD117+ cells in the upper and lower chambers. Spontaneous migration (ca. 5%) was subtracted for all time points. Data are representative of four experiments done in duplicates each. *:p<0.05 and **:p<0.01 as analyzed by ANOVA test followed by Tukey's test.

Mentions: After observing MCs strongly attached to both, human primary first trimester trophoblast and JEG-3 cells, we next investigated whether soluble factors released from trophoblasts may attract human MCs. We therefore performed migration assays by using the well-documented transwell method between HMC-1 cells on the upper side and human primary trophoblast cells or JEG-3 cells in the bottom, both separated by a 8 µm thick transwell. As shown in Fig. 2, HMC-1 cells strongly migrated towards both, human first trimester trophoblast cells (Fig. 2A) and JEG-3 (Fig. 2B) cell line. After 4 h a migration of 40% can be observed, while the highest percentage of migration was observed after 24 h and toward primary trophoblast cells (Fig. 2A). This point out that trophoblasts actively attract MCs. This may occur under hormonal regulation as the placenta is a main source of estrogen and progesterone. To understand whether MCs are also attracted to uterine tissue after hormonal changes, e.g. during menstrual cycle, we additionally tested the capacity of the uterine cells to induce the migration of MCs under hormonal influence. We stimulated AN3-CA cells with E2 and P4 and analyzed the migration of HMC-1 cells by using migration assay. HMC-1 cells strongly migrated toward E2 + P4-treated human uterine cells (AN3-CA) as shown in Fig. 2C. The highest percentage of migration was observed after 24 h of culture (22%). Our data confirm that MCs can migrate to both, uterus and fetal-maternal interface. We next concentrated on the mechanisms of migration of MCs to the uterus and fetal-maternal interface upon hormonal influences.


Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation.

Jensen F, Woudwyk M, Teles A, Woidacki K, Taran F, Costa S, Malfertheiner SF, Zenclussen AC - PLoS ONE (2010)

Human MCs actively migrate towards human trophoblast cells as well as to uterine cells treated with hormones.Using a two-chamber trans-well system, the migration of HMC-1 cells to primary first trimester trophoblasts (Fig. 2A) or JEG-3 cells (Fig. 2B) as well as to uterine cell line (AN3-CA) (Fig. 2C) upon hormonal treatment was analyzed at different time points (0, 4, 8, 24, and 48 h) by determining the relative number of HMC-1-CD117+ cells present in the lower part of the system referred to the total number of CD117+ cells in the upper and lower chambers. Spontaneous migration (ca. 5%) was subtracted for all time points. Data are representative of four experiments done in duplicates each. *:p<0.05 and **:p<0.01 as analyzed by ANOVA test followed by Tukey's test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008683&req=5

pone-0014409-g002: Human MCs actively migrate towards human trophoblast cells as well as to uterine cells treated with hormones.Using a two-chamber trans-well system, the migration of HMC-1 cells to primary first trimester trophoblasts (Fig. 2A) or JEG-3 cells (Fig. 2B) as well as to uterine cell line (AN3-CA) (Fig. 2C) upon hormonal treatment was analyzed at different time points (0, 4, 8, 24, and 48 h) by determining the relative number of HMC-1-CD117+ cells present in the lower part of the system referred to the total number of CD117+ cells in the upper and lower chambers. Spontaneous migration (ca. 5%) was subtracted for all time points. Data are representative of four experiments done in duplicates each. *:p<0.05 and **:p<0.01 as analyzed by ANOVA test followed by Tukey's test.
Mentions: After observing MCs strongly attached to both, human primary first trimester trophoblast and JEG-3 cells, we next investigated whether soluble factors released from trophoblasts may attract human MCs. We therefore performed migration assays by using the well-documented transwell method between HMC-1 cells on the upper side and human primary trophoblast cells or JEG-3 cells in the bottom, both separated by a 8 µm thick transwell. As shown in Fig. 2, HMC-1 cells strongly migrated towards both, human first trimester trophoblast cells (Fig. 2A) and JEG-3 (Fig. 2B) cell line. After 4 h a migration of 40% can be observed, while the highest percentage of migration was observed after 24 h and toward primary trophoblast cells (Fig. 2A). This point out that trophoblasts actively attract MCs. This may occur under hormonal regulation as the placenta is a main source of estrogen and progesterone. To understand whether MCs are also attracted to uterine tissue after hormonal changes, e.g. during menstrual cycle, we additionally tested the capacity of the uterine cells to induce the migration of MCs under hormonal influence. We stimulated AN3-CA cells with E2 and P4 and analyzed the migration of HMC-1 cells by using migration assay. HMC-1 cells strongly migrated toward E2 + P4-treated human uterine cells (AN3-CA) as shown in Fig. 2C. The highest percentage of migration was observed after 24 h of culture (22%). Our data confirm that MCs can migrate to both, uterus and fetal-maternal interface. We next concentrated on the mechanisms of migration of MCs to the uterus and fetal-maternal interface upon hormonal influences.

Bottom Line: Mast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus.Moreover, MC degranulation correlates with angiogenesis during pregnancy.By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation.

View Article: PubMed Central - PubMed

Affiliation: Experimental Obstetrics & Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. federico.jensen@med.ovgu.de

ABSTRACT

Background: Mast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus. Moreover, MC degranulation correlates with angiogenesis during pregnancy. The number of MCs in the uterus has been shown to fluctuate during menstrual cycle in human and estrus cycle in rat and mouse indicating a hormonal influence on their recruitment from the periphery to the uterus. However, the mechanisms behind MC migration to the uterus are still unknown.

Methodology/principal findings: We first utilized migration assays to show that MCs are able to migrate to the uterus and to the fetal-maternal interface upon up-regulation of the expression of chemokine receptors by hormonal changes. By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation.

Conclusion/significance: We propose that estradiol and progesterone modulate the migration of MCs from the periphery to the uterus and their degranulation, which may prepare the uterus for implantation.

Show MeSH