Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy

Abstract

Human chorionic gonadotrophin (hCG) is released within hours of fertilization and has a profound ability to downregulate maternal cellular immunity against trophoblastic paternal antigens. It also promotes angiogenic activity of the extravillous trophoblast, and impairment of this function may lead to inadequate placentation and an increased risk of preeclampsia. There is increasing evidence that hCG alters the activity of dendritic cells via an upregulation of indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine production, as well as encouraging Treg cell recruitment to the fetal-maternal interface. These changes are critical in promoting maternal tolerance. hCG is also able to increase the proliferation of uterine natural killer cells, while reducing the activity of cytotoxic peripheral blood natural killer cells. There are rare reports of autoantibodies directed against hCG or the luteinizing hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies are more frequent in women with thyroid autoimmunity. This may explain the association between thyroid autoimmunity and impaired fertility. Downregulating these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be helpful in some women with early miscarriage or recurrent failed in vitro fertilization.

Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal-maternal interface

“…Indeed, it is essential for the prolongation of corpus luteal function and hence progesterone synthesis until the placenta takes over. The many functions of hCG relating to placental growth, invasion, angiogenesis and the regulation of maternal immune tolerance of the placenta and fetus are well described (for reviews see Norris et al , 2011; Bansal et al , 2012). Lowered CGB expression in the placenta has also been observed in miscarriages, and is higher in ectopic, molar and growth-restricted pregnancies (McCarthy et al , 2007; Rull et al , 2008).…”

The Endocrine Milieu and CD4 T-Lymphocyte Polarization during Pregnancy

“…Particularly, uNK cells contribute to essential vascular changes by regulating the remodeling of decidual spiral arterioles (119, 120) and by secreting angiogenic factors as members of VEGF family (121). It has been shown that hCG regulates uNK proliferation (122). A dose-dependant increase in uNK proliferation is observed when isolated human uNK are incubated with hCG (123).…”

Elevated expression of glucocorticoid-induced leucine zipper in placental endothelial and trophoblastic cells in preeclampsia

“…Increasing immune activity medium in physiological levels is observedduring pregnancy. [21][22][23] However, the deterioration of this balance is associated with pregnancy complications. [21][22][23] It is not known whether the increase in GILZ level in trophoblasts and endothelial cellsis a protective reaction or has a pathological role in PE.…”

“…[21][22][23] However, the deterioration of this balance is associated with pregnancy complications. [21][22][23] It is not known whether the increase in GILZ level in trophoblasts and endothelial cellsis a protective reaction or has a pathological role in PE. Previous studies have shown that GILZ release increased with gestational age and it had a role in COX-2 andprostagland in synthesis.…”