Human Chorionic Gonadotropin and Early Embryogenesis: Review

Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglyco- sylated hCG, free β subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi- effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function

Implantation Failure in Endometriosis Patients: Etiopathogenesis

peer reviewedEmbryo implantation requires adequate dialogue between a good quality embryo and a receptive endometrium. This implantation is still considered as the black box of reproductive medicine. Endometriosis is a highly prevalent chronic inflammatory disease, concerning about 10% of women of reproductive age and is one of the major causes of female infertility. The mechanisms involved in endometriosis-related infertility, an event not yet completely understood, are multifactorial and include anatomical changes, reduction in ovarian reserve, endocrine abnormalities, genetic profile, immunity markers, inflammatory mediators, or altered endometrial receptivity. In this article, we will focus on the impact of endometriosis on embryo quality and on endometrial receptivity. Results: Poor oocyte and embryo quality seem to promote a lower pregnancy rate, more than the endometrium itself in women with endometriosis. Other studies report the contrary. In addition, hormonal imbalance observed in the endometrium could also alter the embryo implantation. Conclusion: Controversial results in the literature add difficulties to the understanding of the mechanisms that lead to embryo implantation disorders. Furthermore, either oocyte/embryo impairment, altered endometrium, or both may cause impaired implantation. New prospective, randomized, and controlled studies are necessary to determine the origin of the defects that make conception more difficult in the case of endometriosis and adenomyosis

Human chorionic gonadotrophin (hCG): new pleiotropic functions for an "old" hormone during pregnancy

peer reviewedaudience: researcher, professionalHuman chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hcg RNA is transcribed as early as the 8-cell stage and the blastocyst produces the protein before its implantation. hCG in the uterine microenvironment binds with its cognate receptor LHCGR on the endometrial surface. This binding stimulates LIF production and inhibits IL-6 production by epithelial cells of the endometrium. These effects ensure essential help in the preparation of the endometrium for initial embryo implantation. hCG also effects angiogenic and immunomodulatory actions as reported in many articles by our laboratories and other ones. By stimulating angiogenesis and vasculogenesis, hCG provides the placenta with an adequate maternal blood supply and optimal embryo nutrition during the invasion of the uterine endometrium. The immunomodulatory properties of hCG are numerous and important for programming maternal immune tolerance towards the embryo. The reported effects of hCG on uterine NK, Treg and B cells, three major cell populations for the maintenance of pregnancy, demonstrate the role of this embryonic signal as a crucial immune regulator in the course of pregnancy. Human embryo rejection for hCG-related immunological reasons has been studied in different ways, and a sufficient dose of hCG seems to be necessary to maintain maternal tolerance. Different teams have studied the addition of hCG in patients suffering from recurrent miscarriages or implantation failures. HCG could also have a beneficial or a negative impact on autoimmune diseases during pregnancy. In this review, we will discuss the immunological impacts hCG during pregnancy and if this hormone might be used therapeutically

Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.

The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation

The Endocrine Milieu and CD4 T-Lymphocyte Polarization during Pregnancy

Acceptance of the fetal semi-allograft by the mother’s immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+ regulatory T (Treg) and Th17 cells. Pregnancy hormones exert very significant modulatory properties on the maternal immune system. In this review, we describe mechanisms by which the endocrine milieu modulates CD4 T-cell polarisation during pregnancy. We first focused on Treg and Th17 cells and on their importance for pregnancy. Secondly, we review the effects of pregnancy hormones (progesterone, estradiol) on immune cells previously described, with a particular attention to human chorionic gonadotropin (hCG). The importance of Treg cells for pregnancy is evidenced. They are recruited before implantation and are essential for pregnancy maintenance. Decreased number or less efficient Treg cells are implicated in fertility disorders. As for Th17 cells, the few available studies suggest that they have a negative impact on fertility. Th17 frequency is increased in infertile patients. With the combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and Th17 cells, P4 contributes to establishment of a favorable environment for pregnancy. E2 effects are more dependent on the context but it seems that E2 promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively influences activities of Treg and uNK cells. This embryo signal is an essential actor for the success of pregnancy, both as the endocrine factor regulating P4 secretion by the ovarian corpus luteum, but also as a paracrine agent during implantation as well as an angiogenic and immunologic mediator during the course of gestation. LH immune properties begin to be studied but its positive impact on Treg cells suggests that LH could be a considerable immunomodulator in the mouse