Experimental Obstetrics & Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
PLoS One. 2010 Dec 22;5(12):e14409. doi: 10.1371/journal.pone.0014409.
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.
基于肥大细胞(MCs)脱颗粒会导致关键因子(如组胺、MMPs、类胰蛋白酶和 VEGF)释放这一事实,MCs 一直被怀疑是着床的重要参与者,这些因子已知参与胚胎附着和向子宫内的后续入侵。此外,MC 脱颗粒与怀孕期间的血管生成有关。已经表明,人类的月经周期和大鼠、小鼠的动情周期中,子宫内的 MC 数量会波动,这表明激素对它们从外周招募到子宫有影响。然而,MC 迁移到子宫的机制仍不清楚。
方法/主要发现:我们首先利用迁移实验表明,MC 能够迁移到子宫和胎儿-母体界面,这是通过激素变化上调趋化因子受体的表达实现的。通过使用卵巢切除术动物模型,我们提供了明确的证据,表明体内雌激素和孕激素也会吸引 MC 进入子宫,并进一步促使它们成熟和脱颗粒。
结论/意义:我们提出,雌激素和孕激素调节 MC 从外周向子宫的迁移及其脱颗粒,这可能为着床做准备。