Interferon‐γ inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels

Lash, Gendie E.; Otun, Harry A.; Innes, Barbara A.; Kirkley, Maureen; Oliveira, Leandro De; Searle, Roger F.; Robson, Stephen C.; Bulmer, Judith N.

doi:10.1096/fj.06-6616com

Cited by 155 publications

(114 citation statements)

References 43 publications

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“…Reports have both supported and refuted a direct role for IFNG in regulation of EVT behaviour. We have recently demonstrated that IFNG regulates EVT invasion via mechanisms dependent on increased EVT apoptosis as well as decreased protease activity (Lash et al 2006b). By contrast, a report examining EVT column formation and migration found IFNG to only partially regulate EVT (Hu et al 2006).…”

Section: Discussionmentioning

confidence: 93%

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Williams¹,

Bulmer²,

Searle³

et al. 2009

Reproduction

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Alterations in the balance of leucocyte populations in uterine decidua may lead to the generation of an unfavourable cytokine environment that is associated with unsuccessful pregnancy. Single and double immunohistochemical labelling was used to examine leucocyte populations in decidua from normal third trimester, foetal growth-restricted and pre-eclamptic pregnancies. Placental bed biopsies from 12 women undergoing elective Caesarean section with no hypertension or foetal growth restriction (FGR), 8 women with FGR without maternal hypertension and 12 women with pre-eclampsia (PE) were used to quantify decidual CD56C uterine NK cells, CD14C macrophages, CD3CT-lymphocytes and CD8C lymphocytes. CD3CCD56C, CD8CCD56C and CD161CCD3C double-labelled cells in decidua were compared in PE and control decidua. Decidual CD3CT-lymphocytes (P!0.01), CD8C cytotoxic T-lymphocytes (P!0.05), CD14C macrophages (P!0.0001) and CD56C uterine natural killer (uNK) cells (PZ0.01) were decreased in placental bed biopsies from women with PE compared with control third trimester decidua. By contrast, only CD56C uNK cells were decreased in FGR decidua (P!0.05). Double-positive CD8CCD56C cells were also decreased in PE compared with control third trimester decidua (P!0.05). The reduction in specific leucocyte subset numbers in PE and uNK cells in FGR suggests that altered local cytokine balance may be important in defective trophoblast invasion and spiral artery transformation in these pathological pregnancies.

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Section: Discussionmentioning

confidence: 93%

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Williams¹,

Bulmer²,

Searle³

et al. 2009

Reproduction

149

113

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“…uNK cells produce a range of cytokines that have been shown to regulate trophoblast invasion; these include TNF-α, TGF-β1 and IFN-γ, all of which inhibit trophoblast invasion from placental explants (Otun et al, 2003;Lash et al, 2005;Lash et al, 2006a). Recently, Hanna et al (2006) demonstrated that uNK cell supernatants could stimulate isolated cytotrophoblast invasion through matrigel in a mechanism that was partly dependent on IL-8 and IP-10.…”

Section: Functional Investigationsmentioning

confidence: 99%

Immune cells in the placental bed

Bulmer¹,

Williams²,

Lash³

2010

Int. J. Dev. Biol.

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“…Furthermore, IFNG is targeted to heparan sulfate that is essential for implantation in mice (Kirn-Safran et al 2008), and this may protect IFNG from inactivation and increase its stability (Lortart-Jacob & Grimaud 1991) to allow protracted effects of IFNG on vascular development in decidual tissue. Type I and type II IFNs modify gene expression at implantation sites in rodents to affect the conceptus directly or to exert indirect effects through actions on blood vessels and decidual cells required for successful implantation and pregnancy (Lash et al 2006). …”

Section: Comparative Aspects Of Implantationmentioning

confidence: 99%

Comparative aspects of implantation

Bazer

Spencer²,

Johnson³

et al. 2009

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Uterine receptivity to implantation of blastocysts in mammals includes hatching from zona pellucida, precontact with uterine luminal (LE) and superficial glandular (sGE) epithelia and orientation of blastocyst, apposition between trophectoderm and uterine LE and sGE, adhesion of trophectoderm to uterine LE/sGE, and, in some species, limited or extensive invasion into the endometrial stroma and induction of decidualization of stromal cells. These peri-implantation events are prerequisites for pregnancy recognition signaling, implantation, and placentation required for fetal-placental growth and development through the remainder of pregnancy. Although there is a range of strategies for implantation in mammals, a common feature is the requirement for progesterone (P 4 ) to downregulate expression of its receptors in uterine epithelia and P 4 prior to implantation events. P 4 then mediates its effects via growth factors expressed by stromal cells in most species; however, uterine luminal epithelium may express a growth factor in response to P 4 and/or estrogens in species with a true epitheliochorial placenta. There is also compelling evidence that uterine receptivity to implantation involves temporal and cell-specific expression of interferon (IFN)-stimulated genes that may be induced directly by an IFN or induced by P 4 and stimulated by an IFN. These genes have many roles including nutrient transport, cellular remodeling, angiogenesis and relaxation of vascular tissues, cell proliferation and migration, establishment of an antiviral state, and protection of conceptus tissues from challenges by the maternal immune cells.

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Interferon‐γ inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels

Abstract: uNK cells are a source of IFN-gamma within early human pregnancy decidua. Mechanisms of IFN-gamma inhibition of EVT invasion include both increased EVT apoptosis and reduced levels of active proteases.

Cited by 155 publications

References 43 publications

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Immune cells in the placental bed

Comparative aspects of implantation

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