Abstract
Human chorionic gonadotropin (hCG) serves as one of the first signals provided by the embryo to the mother. Exactly at the time when the first step of the implantation process is initiated and the blastocyst adheres to the maternal endometrium, the embryonic tissue starts to actively secrete hCG. Shortly thereafter, the hormone can be detected in the maternal circulation where its concentration steadily increases throughout early pregnancy as it is continuously released by the forming placenta. Accumulating evidence underlines the critical function of hCG for embryo implantation and placentation. hCG not only regulates biological aspects of these early pregnancy events but also supports maternal immune cells in their function as helpers in the establishment of an adequate embryo-endometrial relationship. In view of its early presence in the maternal circulation, hCG has the potential to influence both local uterine immune cell populations as well as peripheral ones. The current review aims to summarize recent literature on the participation of innate and adaptive immune cells in embryo implantation and placentation with a specific focus on their regulation by hCG.
Highlights
Within a few days, after fertilization of the oocyte took place in the fallopian tube, the early embryo in its morula stage enters the uterine cavity
Its major function is to induce proliferation and invasion of cytotrophoblast cells and it has been reported that H-Human chorionic gonadotropin (hCG) proportions higher than 50% of total hCG are required for successful embryo implantation [28] (Figure 1B)
We showed that female mice devoid of mast cells (MCs) were either completely incapable to implant or implanted but showed insufficient Uterine spiral arteries (uSA) remodeling and abnormal placentation [100] resulting in intrauterine growth restriction (IUGR) [101] (Figure 1D)
Summary
After fertilization of the oocyte took place in the fallopian tube, the early embryo in its morula stage enters the uterine cavity. Its major function is to induce proliferation and invasion of cytotrophoblast cells and it has been reported that H-hCG proportions higher than 50% of total hCG are required for successful embryo implantation [28] (Figure 1B). Yu et al [61] further indicated that hCG-activated PBMCs significantly augmented MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expression in human trophoblast cells These findings let assume that hCG administration to patients undergoing ART will support pregnancy in two steps that involve the maternal immune system. HCG will activate immigrated and residual immune cell populations in the pre-implantation phase to support these cells in promoting embryo attachment and invasion as well as in forcing the decidualization process. HCG may control neutrophil function as their excessive activation was proven in adverse pregnancy outcomes such as fetal loss and PE [67, 76]
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