Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells

Fluhr, Herbert; Bischof-Islami, Dorina; Krenzer, Stefanie; Licht, Peter B.; Bischof, P.; Zygmunt, Marek

doi:10.1016/j.fertnstert.2007.08.023

Cited by 51 publications

(30 citation statements)

References 45 publications

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“…Our results showed that knockdown of OPN was able to inhibit the trophoblast-spreading area in the mESCs. During decidualization, the stroma undergoes comprehensive ECM degradation and reconstruction, a process that relies on the balance of MMPs and TIMPs [47], [48]. The matrix metalloproteinases are a group of zinc-containing, extracellular matrix proteases that play important roles in tissue remodeling, inflammation, fibrosis, and activation of various latent cytokines and cell adhesion molecules.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Is Expressed in the Mouse Uterus during Early Pregnancy and Promotes Mouse Blastocyst Attachment and Invasion In Vitro

Xie

Liu

et al. 2014

PLoS ONE

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Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are induced by in vivo and in vitro decidualization. OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion.

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Section: Discussionmentioning

confidence: 99%

Osteopontin Is Expressed in the Mouse Uterus during Early Pregnancy and Promotes Mouse Blastocyst Attachment and Invasion In Vitro

Xie

Liu

et al. 2014

PLoS ONE

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“…hCG is produced by differentiated syncytiotrophoblasts and its main function is to stimulate P4 production by the corpus luteum (20). Moreover, hCG supports pregnancy by facilitating trophoblast invasion (21–23), promoting angiogenesis, and ensuring nourishment of the fetus (24–26). In rodents, similar functions are mediated by the highly homologous LH.…”

Section: Human Chorionic Gonadotropinmentioning

confidence: 99%

Endocrine Factors Modulating Immune Responses in Pregnancy

2014

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How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.

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“…After reaching its maximum level between the 9th and 12th weeks of pregnancy, hCG concentrations decline until birth (9). In addition to its main function in stimulating P production by the corpus luteum, hCG has been described to facilitate trophoblast invasion (10)(11)(12), support angiogenesis, and ensure nourishment of the fetus (13)(14)(15). In the 1970s and 1980s, several studies suggested hCG as an important factor modulating T and B cell responses (16,17) via the induction of the at that time called suppressor T cells (18).…”

mentioning

confidence: 99%

Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance

Schumacher

Heinze

Witte

et al. 2013

The Journal of Immunology

142

138

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Normal pregnancy is characterized by an early expansion of regulatory T cells (Tregs), which is known to contribute to fetal tolerance. However, mechanisms and factors behind Treg expansion are not yet defined. Recently, we proposed that the pregnancy hormone human chorionic gonadotropin (hCG) efficiently attracts human Tregs to trophoblasts, favoring their accumulation locally. In this study, we hypothesized that hCG not only acts as a chemoattractant of Tregs but also plays a central role in pregnancy-induced immune tolerance. Virgin, normal pregnant, and abortion-prone female mice were treated either with 10 IU/ml hCG or PBS at days 0, 2, 4, and 6 of pregnancy. The hCG effect on Treg frequency and cytokine secretion was determined in Foxp3gfp females. hCG impact on Treg suppressive capacity was studied in vitro. In vivo, we investigated whether hCG enhances Treg suppressive capacity indirectly by modulating dendritic cell maturation in an established mouse model of disturbed fetal tolerance. Application of hCG increased Treg frequency in vivo and their suppressive activity in vitro. In females having spontaneous abortions, hCG provoked not only an augmentation of Treg numbers, but also normalized fetal abortion rates. hCG-generated Tregs were fully functional and could confer tolerance when adoptively transferred. hCG also retained dendritic cells in a tolerogenic state that is likely to contribute to both Treg expansion and prevention of abortion. Our results position hCG in a novel, so far unknown role as modulator of immune tolerance during pregnancy.

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Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells

Cited by 51 publications

References 45 publications

Osteopontin Is Expressed in the Mouse Uterus during Early Pregnancy and Promotes Mouse Blastocyst Attachment and Invasion In Vitro

Osteopontin Is Expressed in the Mouse Uterus during Early Pregnancy and Promotes Mouse Blastocyst Attachment and Invasion In Vitro

Endocrine Factors Modulating Immune Responses in Pregnancy

Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance

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